DNA

Last updated

The structure of the DNA double helix. The atoms in the structure are colour-coded by element and the detailed structures of two base pairs are shown in the bottom right. DNA Structure+Key+Labelled.pn NoBB.png
The structure of the DNA double helix. The atoms in the structure are colour-coded by element and the detailed structures of two base pairs are shown in the bottom right.
The structure of part of a DNA double helix ADN animation.gif
The structure of part of a DNA double helix

Deoxyribonucleic acid ( /dˈɒksɪˌrbnjˌklɪk, -ˌkl-/ ( Loudspeaker.svg listen ); [1] DNA) is a molecule composed of two chains that coil around each other to form a double helix carrying genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses. DNA and ribonucleic acid (RNA) are nucleic acids; alongside proteins, lipids and complex carbohydrates (polysaccharides), nucleic acids are one of the four major types of macromolecules that are essential for all known forms of life.

Nucleic acid double helix The structure formed by double-stranded molecules of nucleic acids such as DNA.

In molecular biology, the term double helix refers to the structure formed by double-stranded molecules of nucleic acids such as DNA. The double helical structure of a nucleic acid complex arises as a consequence of its secondary structure, and is a fundamental component in determining its tertiary structure. The term entered popular culture with the publication in 1968 of The Double Helix: A Personal Account of the Discovery of the Structure of DNA by James Watson.

Genetics Science of genes, heredity, and variation in living organisms

Genetics is a branch of biology concerned with the study of genes, genetic variation, and heredity in organisms.

Reproduction the production of new individuals that contain some portion of genetic material inherited from one or more parent organisms

Reproduction is the biological process by which new individual organisms – "offspring" – are produced from their "parents". Reproduction is a fundamental feature of all known life; each individual organism exists as the result of reproduction. There are two forms of reproduction: asexual and sexual.

Contents

The two DNA strands are also known as polynucleotides as they are composed of simpler monomeric units called nucleotides. [2] [3] Each nucleotide is composed of one of four nitrogen-containing nucleobases (cytosine [C], guanine [G], adenine [A] or thymine [T]), a sugar called deoxyribose, and a phosphate group. The nucleotides are joined to one another in a chain by covalent bonds between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. The nitrogenous bases of the two separate polynucleotide strands are bound together, according to base pairing rules (A with T and C with G), with hydrogen bonds to make double-stranded DNA. The complementary nitrogenous bases are divided into two groups, pyrimidines and purines. In DNA, the pyrimidines are thymine and cytosine; the purines are adenine and guanine.

A polynucleotide molecule is a biopolymer composed of 13 or more nucleotide monomers covalently bonded in a chain. DNA and RNA are examples of polynucleotides with distinct biological function. The prefix poly comes from the ancient Greek πολυς. DNA consists of two chains of polynucleotides, with each chain in the form of a helical spiral.

A monomer is a molecule that "can undergo polymerization thereby contributing constitutional units to the essential structure of a macromolecule". Large numbers of monomers combine to form polymers in a process called polymerization.

Nucleotide biological molecules that form the building blocks of nucleic acids

Nucleotides are organic molecules that serve as the monomer units for forming the nucleic acid polymers deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules within all life-forms on Earth. Nucleotides are the building blocks of nucleic acids; they are composed of three sub unit molecules: a nitrogenous base, a five-carbon sugar, and at least one phosphate group.

Both strands of double-stranded DNA store the same biological information. This information is replicated as and when the two strands separate. A large part of DNA (more than 98% for humans) is non-coding, meaning that these sections do not serve as patterns for protein sequences. The two strands of DNA run in opposite directions to each other and are thus antiparallel. Attached to each sugar is one of four types of nucleobases (informally, bases). It is the sequence of these four nucleobases along the backbone that encodes genetic information. RNA strands are created using DNA strands as a template in a process called transcription. Under the genetic code, these RNA strands specify the sequence of amino acids within proteins in a process called translation.

DNA replication The cellular metabolic process in which a cell duplicates one or more molecules of DNA. DNA replication begins when specific sequences, known as origins of replication, are recognized and bound by initiation proteins

In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the basis for biological inheritance. The cell possesses the distinctive property of division, which makes replication of DNA essential.

Noncoding DNA sequences are components of an organism's DNA that do not encode protein sequences. Some noncoding DNA is transcribed into functional non-coding RNA molecules. Other functions of noncoding DNA include the transcriptional and translational regulation of protein-coding sequences, scaffold attachment regions, origins of DNA replication, centromeres and telomeres.

In biochemistry, two biopolymers are antiparallel if they run parallel to each other but with opposite directionality (alignments). An example is the two complementary strands of a DNA double helix, which run in opposite directions alongside each other.

Within eukaryotic cells, DNA is organized into long structures called chromosomes. Before typical cell division, these chromosomes are duplicated in the process of DNA replication, providing a complete set of chromosomes for each daughter cell. Eukaryotic organisms (animals, plants, fungi and protists) store most of their DNA inside the cell nucleus as nuclear DNA, and some in the mitochondria as mitochondrial DNA or in chloroplasts as chloroplast DNA. [4] In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm, in circular chromosomes. Within eukaryotic chromosomes, chromatin proteins, such as histones, compact and organize DNA. These compacting structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.

Chromosome DNA molecule containing genetic material of a cell

A chromosome is a deoxyribonucleic acid (DNA) molecule with part or all of the genetic material (genome) of an organism. Most eukaryotic chromosomes include packaging proteins which, aided by chaperone proteins, bind to and condense the DNA molecule to prevent it from becoming an unmanageable tangle.

Cell division The process resulting in division and partitioning of components of a cell to form more cells; may or may not be accompanied by the physical separation of a cell into distinct, individually membrane-bounded daughter cells.

Cell division is the process by which a parent cell divides into two or more daughter cells. Cell division usually occurs as part of a larger cell cycle. In eukaryotes, there are two distinct types of cell division: a vegetative division, whereby each daughter cell is genetically identical to the parent cell (mitosis), and a reproductive cell division, whereby the number of chromosomes in the daughter cells is reduced by half to produce haploid gametes (meiosis). Meiosis results in four haploid daughter cells by undergoing one round of DNA replication followed by two divisions. Homologous chromosomes are separated in the first division, and sister chromatids are separated in the second division. Both of these cell division cycles are used in the process of sexual reproduction at some point in their life cycle. Both are believed to be present in the last eukaryotic common ancestor.

Eukaryote taxonomic group whose members have complex structures enclosed within membranes

Eukaryotes are organisms whose cells have a nucleus enclosed within membranes, unlike prokaryotes, which have no membrane-bound organelles. Eukaryotes belong to the domain Eukaryota or Eukarya. Their name comes from the Greek εὖ and κάρυον. Eukaryotic cells also contain other membrane-bound organelles such as mitochondria and the Golgi apparatus, and in addition, some cells of plants and algae contain chloroplasts. Unlike unicellular archaea and bacteria, eukaryotes may also be multicellular and include organisms consisting of many cell types forming different kinds of tissue. Animals and plants are the most familiar eukaryotes.

DNA was first isolated by Friedrich Miescher in 1869. Its molecular structure was first identified by Francis Crick and James Watson at the Cavendish Laboratory within the University of Cambridge in 1953, whose model-building efforts were guided by X-ray diffraction data acquired by Raymond Gosling, who was a post-graduate student of Rosalind Franklin. DNA is used by researchers as a molecular tool to explore physical laws and theories, such as the ergodic theorem and the theory of elasticity. The unique material properties of DNA have made it an attractive molecule for material scientists and engineers interested in micro- and nano-fabrication. Among notable advances in this field are DNA origami and DNA-based hybrid materials. [5]

Friedrich Miescher Swiss biochemist

Johannes Friedrich Miescher was a Swiss physician and biologist. He was the first researcher to isolate nucleic acid.

Francis Crick British molecular biologist, biophysicist, neuroscientist; co-discoverer of the structure of DNA

Francis Harry Compton Crick was a British molecular biologist, biophysicist, and neuroscientist. In 1953, he co-authored with James Watson the academic paper proposing the double helix structure of the DNA molecule. Together with Watson and Maurice Wilkins, he was jointly awarded the 1962 Nobel Prize in Physiology or Medicine "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material". The results were based partly on fundamental studies done by Rosalind Franklin, Raymond Gosling and Wilkins.

James Watson American molecular biologist, geneticist, and zoologist

James Dewey Watson is an American molecular biologist, geneticist and zoologist. In 1953, he co-authored with Francis Crick the academic paper proposing the double helix structure of the DNA molecule. Watson, Crick, and Maurice Wilkins were awarded the 1962 Nobel Prize in Physiology or Medicine "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material".

Properties

Chemical structure of DNA; hydrogen bonds shown as dotted lines DNA chemical structure.svg
Chemical structure of DNA; hydrogen bonds shown as dotted lines

DNA is a long polymer made from repeating units called nucleotides. [6] [7] The structure of DNA is dynamic along its length, being capable of coiling into tight loops and other shapes. [8] In all species it is composed of two helical chains, bound to each other by hydrogen bonds. Both chains are coiled around the same axis, and have the same pitch of 34  angstroms (Å) (3.4  nanometres). The pair of chains has a radius of 10 angstroms (1.0 nanometre). [9] According to another study, when measured in a different solution, the DNA chain measured 22 to 26 angstroms wide (2.2 to 2.6 nanometres), and one nucleotide unit measured 3.3 Å (0.33 nm) long. [10] Although each individual nucleotide is very small, a DNA polymer can be very large and contain hundreds of millions, such as in chromosome 1. Chromosome 1 is the largest human chromosome with approximately 220 million base pairs, [11] and would be 85 mm long if straightened.

Polymer substance composed of macromolecules with repeating structural units

A polymer is a large molecule, or macromolecule, composed of many repeated subunits. Due to their broad range of properties, both synthetic and natural polymers play essential and ubiquitous roles in everyday life. Polymers range from familiar synthetic plastics such as polystyrene to natural biopolymers such as DNA and proteins that are fundamental to biological structure and function. Polymers, both natural and synthetic, are created via polymerization of many small molecules, known as monomers. Their consequently large molecular mass relative to small molecule compounds produces unique physical properties, including toughness, viscoelasticity, and a tendency to form glasses and semicrystalline structures rather than crystals. The terms polymer and resin are often synonymous with plastic.

Angstrom unit of length; equals 0.1 nanometre

The angstrom or ångström is a unit of length equal to 10−10 m; that is, one ten-billionth of a metre, 0.1 nanometre, or 100 picometres. Its symbol is Å, a letter of the Swedish alphabet.

The nanometre or nanometer is a unit of length in the metric system, equal to one billionth of a metre. The name combines the SI prefix nano- with the parent unit name metre. It can be written in scientific notation as 1×10−9 m, in engineering notation as 1 E−9 m, and as simply 1/1000000000 metres. When used as a prefix for something other than a unit of measure, nano refers to nanotechnology, or phenomena typically occurring on a scale of nanometres.

DNA does not usually exist as a single strand, but instead as a pair of strands that are held tightly together. [9] [12] These two long strands coil around each other, in the shape of a double helix. The nucleotide contains both a segment of the backbone of the molecule (which holds the chain together) and a nucleobase (which interacts with the other DNA strand in the helix). A nucleobase linked to a sugar is called a nucleoside, and a base linked to a sugar and to one or more phosphate groups is called a nucleotide. A biopolymer comprising multiple linked nucleotides (as in DNA) is called a polynucleotide. [13]

The backbone of the DNA strand is made from alternating phosphate and sugar residues. [14] The sugar in DNA is 2-deoxyribose, which is a pentose (five-carbon) sugar. The sugars are joined together by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings. These are known as the 3-end (three prime end), and 5-end (five prime end) carbons, the prime symbol being used to distinguish these carbon atoms from those of the base to which the deoxyribose forms a glycosidic bond. When imagining DNA, each phosphoryl is normally considered to "belong" to the nucleotide whose 5′ carbon forms a bond therewith. Any DNA strand therefore normally has one end at which there is a phosphoryl attached to the 5′ carbon of a ribose (the 5′ phosphoryl) and another end at which there is a free hydroxyl attached to the 3′ carbon of a ribose (the 3′ hydroxyl). The orientation of the 3′ and 5′ carbons along the sugar-phosphate backbone confers directionality (sometimes called polarity) to each DNA strand. In a nucleic acid double helix, the direction of the nucleotides in one strand is opposite to their direction in the other strand: the strands are antiparallel. The asymmetric ends of DNA strands are said to have a directionality of five prime end (5′ ), and three prime end (3′), with the 5′ end having a terminal phosphate group and the 3′ end a terminal hydroxyl group. One major difference between DNA and RNA is the sugar, with the 2-deoxyribose in DNA being replaced by the alternative pentose sugar ribose in RNA. [12]

A section of DNA. The bases lie horizontally between the two spiraling strands (animated version). DNA orbit animated static thumb.png
A section of DNA. The bases lie horizontally between the two spiraling strands (animated version).

The DNA double helix is stabilized primarily by two forces: hydrogen bonds between nucleotides and base-stacking interactions among aromatic nucleobases. [16] In the cytosol of the cell, the conjugated pi bonds of nucleotide bases align perpendicular to the axis of the DNA molecule, minimizing their interaction with the solvation shell. The four bases found in DNA are adenine (A), cytosine (C), guanine (G) and thymine (T). These four bases are attached to the sugar-phosphate to form the complete nucleotide, as shown for adenosine monophosphate. Adenine pairs with thymine and guanine pairs with cytosine, forming A-T and G-C base pairs. [17] [18]

Nucleobase classification

The nucleobases are classified into two types: the purines, A and G, which are fused five- and six-membered heterocyclic compounds, and the pyrimidines, the six-membered rings C and T. [12] A fifth pyrimidine nucleobase, uracil (U), usually takes the place of thymine in RNA and differs from thymine by lacking a methyl group on its ring. In addition to RNA and DNA, many artificial nucleic acid analogues have been created to study the properties of nucleic acids, or for use in biotechnology. [19]

Non-canonical bases

Uracil is not usually found in DNA, occurring only as a breakdown product of cytosine. However, in several bacteriophages, such as Bacillus subtilis phages PBS1 and PBS2 and Yersinia phage piR1-37, thymine has been replaced by uracil. [20] Another phage—Staphylococcal phage S6—has been identified with a genome where thymine has been replaced by uracil. [21]

Uracil is also found in the DNA of Plasmodium falciparum [22] It is present is relatively small amounts (7–10 uracil residues per million bases).

5-hydroxymethyldeoxyuridine,(hm5dU) is also known to replace thymidine in several genomes including the Bacillus phages SPO1, ϕe, SP8, H1, 2C and SP82. Another modified uracil—5-dihydroxypentauracil—has also been described. [23]

Base J (beta-d-glucopyranosyloxymethyluracil), a modified form of uracil, is also found in several organisms: the flagellates Diplonema and Euglena , and all the kinetoplastid genera. [24] Biosynthesis of J occurs in two steps: in the first step, a specific thymidine in DNA is converted into hydroxymethyldeoxyuridine; in the second, HOMedU is glycosylated to form J. [25] Proteins that bind specifically to this base have been identified. [26] [27] [28] These proteins appear to be distant relatives of the Tet1 oncogene that is involved in the pathogenesis of acute myeloid leukemia. [29] J appears to act as a termination signal for RNA polymerase II. [30] [31]

In 1976, the S-2La bacteriophage, which infects species of the genus Synechocystis , was found to have all the adenosine bases within its genome replaced by 2,6-diaminopurine. [32] In 2016 deoxyarchaeosine was found to be present in the genomes of several bacteria and the Escherichia phage 9g. [33]

Modified bases also occur in DNA. The first of these recognised was 5-methylcytosine, which was found in the genome of Mycobacterium tuberculosis in 1925. [34] The complete replacement of cytosine by 5-glycosylhydroxymethylcytosine in T even phages (T2, T4 and T6) was observed in 1953. [35] In the genomes of Xanthomonas oryzae bacteriophage Xp12 and halovirus FH the full complement of cystosine has been replaced by 5-methylcytosine. [36] [37] 6N-methyladenine was discovered to be present in DNA in 1955. [38] N6-carbamoyl-methyladenine was described in 1975. [39] 7-Methylguanine was described in 1976. [40] N4-methylcytosine in DNA was described in 1983. [41] In 1985 5-hydroxycytosine was found in the genomes of the Rhizobium phages RL38JI and N17. [42] α-putrescinylthymine occurs in both the genomes of the Delftia phage ΦW-14 and the Bacillus phage SP10. [43] α-glutamylthymidine is found in the Bacillus phage SP01 and 5-dihydroxypentyluracil is found in the Bacillus phage SP15.

The reason for the presence of these non canonical bases in DNA is not known. It seems likely that at least part of the reason for their presence in bacterial viruses (phages) is to avoid the restriction enzymes present in bacteria. This enzyme system acts at least in part as a molecular immune system protecting bacteria from infection by viruses.

This does not appear to be the entire story. Four modifications to the cytosine residues in human DNA have been reported. [44] These modifications are the addition of methyl (CH3)-, hydroxymethyl (CH2OH)-, formyl (CHO)- and carboxyl (COOH)- groups. These modifications are thought to have regulatory functions.

Uracil is found in the centromeric regions of at least two human chromosomes (chromosome 6 and chromosome 11). [45]

Listing of non canonical bases found in DNA

Seventeen non canonical bases are known to occur in DNA. Most of these are modifications of the canonical bases plus uracil.

DNA major and minor grooves. The latter is a binding site for the Hoechst stain dye 33258. DNA-ligand-by-Abalone.png
DNA major and minor grooves. The latter is a binding site for the Hoechst stain dye 33258.

Grooves

Twin helical strands form the DNA backbone. Another double helix may be found tracing the spaces, or grooves, between the strands. These voids are adjacent to the base pairs and may provide a binding site. As the strands are not symmetrically located with respect to each other, the grooves are unequally sized. One groove, the major groove, is 22  angstroms (Å) wide and the other, the minor groove, is 12 Å wide. [46] The width of the major groove means that the edges of the bases are more accessible in the major groove than in the minor groove. As a result, proteins such as transcription factors that can bind to specific sequences in double-stranded DNA usually make contact with the sides of the bases exposed in the major groove. [47] This situation varies in unusual conformations of DNA within the cell (see below), but the major and minor grooves are always named to reflect the differences in size that would be seen if the DNA is twisted back into the ordinary B form.

Base pairing

In a DNA double helix, each type of nucleobase on one strand bonds with just one type of nucleobase on the other strand. This is called complementary base pairing. Here, purines form hydrogen bonds to pyrimidines, with adenine bonding only to thymine in two hydrogen bonds, and cytosine bonding only to guanine in three hydrogen bonds. This arrangement of two nucleotides binding together across the double helix is called a Watson-Crick base pair. Another type of base pairing is Hoogsteen base pairing where two hydrogen bonds form between guanine and cytosine. [48] As hydrogen bonds are not covalent, they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can thus be pulled apart like a zipper, either by a mechanical force or high temperature. [49] As a result of this base pair complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. This reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in organisms. [7]

Base pair GC.svg
Base pair AT.svg
Top, a GC base pair with three hydrogen bonds. Bottom, an AT base pair with two hydrogen bonds. Non-covalent hydrogen bonds between the pairs are shown as dashed lines.

The two types of base pairs form different numbers of hydrogen bonds, AT forming two hydrogen bonds, and GC forming three hydrogen bonds (see figures, right). DNA with high GC-content is more stable than DNA with low GC-content.

As noted above, most DNA molecules are actually two polymer strands, bound together in a helical fashion by noncovalent bonds; this double-stranded (dsDNA) structure is maintained largely by the intrastrand base stacking interactions, which are strongest for G,C stacks. The two strands can come apart—a process known as melting—to form two single-stranded DNA (ssDNA) molecules. Melting occurs at high temperature, low salt and high pH (low pH also melts DNA, but since DNA is unstable due to acid depurination, low pH is rarely used).

The stability of the dsDNA form depends not only on the GC-content (% G,C basepairs) but also on sequence (since stacking is sequence specific) and also length (longer molecules are more stable). The stability can be measured in various ways; a common way is the "melting temperature", which is the temperature at which 50% of the ds molecules are converted to ss molecules; melting temperature is dependent on ionic strength and the concentration of DNA. As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determines the strength of the association between the two strands of DNA. Long DNA helices with a high GC-content have stronger-interacting strands, while short helices with high AT content have weaker-interacting strands. [50] In biology, parts of the DNA double helix that need to separate easily, such as the TATAAT Pribnow box in some promoters, tend to have a high AT content, making the strands easier to pull apart. [51]

In the laboratory, the strength of this interaction can be measured by finding the temperature necessary to break the hydrogen bonds, their melting temperature (also called Tm value). When all the base pairs in a DNA double helix melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules have no single common shape, but some conformations are more stable than others. [52]

Sense and antisense

A DNA sequence is called a "sense" sequence if it is the same as that of a messenger RNA copy that is translated into protein. [53] The sequence on the opposite strand is called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both strands can contain both sense and antisense sequences). In both prokaryotes and eukaryotes, antisense RNA sequences are produced, but the functions of these RNAs are not entirely clear. [54] One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing. [55]

A few DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses, blur the distinction between sense and antisense strands by having overlapping genes. [56] In these cases, some DNA sequences do double duty, encoding one protein when read along one strand, and a second protein when read in the opposite direction along the other strand. In bacteria, this overlap may be involved in the regulation of gene transcription, [57] while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome. [58]

Supercoiling

DNA can be twisted like a rope in a process called DNA supercoiling. With DNA in its "relaxed" state, a strand usually circles the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound. [59] If the DNA is twisted in the direction of the helix, this is positive supercoiling, and the bases are held more tightly together. If they are twisted in the opposite direction, this is negative supercoiling, and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that is introduced by enzymes called topoisomerases. [60] These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription and DNA replication. [61]

From left to right, the structures of A, B and Z DNA A-DNA, B-DNA and Z-DNA.png
From left to right, the structures of A, B and Z DNA

Alternative DNA structures

DNA exists in many possible conformations that include A-DNA, B-DNA, and Z-DNA forms, although, only B-DNA and Z-DNA have been directly observed in functional organisms. [14] The conformation that DNA adopts depends on the hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases, the type and concentration of metal ions, and the presence of polyamines in solution. [62]

The first published reports of A-DNA X-ray diffraction patterns—and also B-DNA—used analyses based on Patterson transforms that provided only a limited amount of structural information for oriented fibers of DNA. [63] [64] An alternative analysis was then proposed by Wilkins et al., in 1953, for the in vivo B-DNA X-ray diffraction-scattering patterns of highly hydrated DNA fibers in terms of squares of Bessel functions. [65] In the same journal, James Watson and Francis Crick presented their molecular modeling analysis of the DNA X-ray diffraction patterns to suggest that the structure was a double-helix. [9]

Although the B-DNA form is most common under the conditions found in cells, [66] it is not a well-defined conformation but a family of related DNA conformations [67] that occur at the high hydration levels present in cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular paracrystals with a significant degree of disorder. [68] [69]

Compared to B-DNA, the A-DNA form is a wider right-handed spiral, with a shallow, wide minor groove and a narrower, deeper major groove. The A form occurs under non-physiological conditions in partly dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, and in enzyme-DNA complexes. [70] [71] Segments of DNA where the bases have been chemically modified by methylation may undergo a larger change in conformation and adopt the Z form. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form. [72] These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription. [73]

Alternative DNA chemistry

For many years, exobiologists have proposed the existence of a shadow biosphere, a postulated microbial biosphere of Earth that uses radically different biochemical and molecular processes than currently known life. One of the proposals was the existence of lifeforms that use arsenic instead of phosphorus in DNA. A report in 2010 of the possibility in the bacterium GFAJ-1, was announced, [74] [74] [75] though the research was disputed, [75] [76] and evidence suggests the bacterium actively prevents the incorporation of arsenic into the DNA backbone and other biomolecules. [77]

Quadruplex structures

At the ends of the linear chromosomes are specialized regions of DNA called telomeres. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme telomerase, as the enzymes that normally replicate DNA cannot copy the extreme 3′ ends of chromosomes. [78] These specialized chromosome caps also help protect the DNA ends, and stop the DNA repair systems in the cell from treating them as damage to be corrected. [79] In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence. [80]

DNA quadruplex formed by telomere repeats. The looped conformation of the DNA backbone is very different from the typical DNA helix. The green spheres in the center represent potassium ions. Parallel telomere quadruple.png
DNA quadruplex formed by telomere repeats. The looped conformation of the DNA backbone is very different from the typical DNA helix. The green spheres in the center represent potassium ions.

These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases form a flat plate and these flat four-base units then stack on top of each other, to form a stable G-quadruplex structure. [82] These structures are stabilized by hydrogen bonding between the edges of the bases and chelation of a metal ion in the centre of each four-base unit. [83] Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or several different parallel strands, each contributing one base to the central structure.

In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here, the single-stranded DNA curls around in a long circle stabilized by telomere-binding proteins. [84] At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This triple-stranded structure is called a displacement loop or D-loop. [82]

Branch-dna-single.svg Branch-DNA-multiple.svg
Single branchMultiple branches
Branched DNA can form networks containing multiple branches.

Branched DNA

In DNA, fraying occurs when non-complementary regions exist at the end of an otherwise complementary double-strand of DNA. However, branched DNA can occur if a third strand of DNA is introduced and contains adjoining regions able to hybridize with the frayed regions of the pre-existing double-strand. Although the simplest example of branched DNA involves only three strands of DNA, complexes involving additional strands and multiple branches are also possible. [85] Branched DNA can be used in nanotechnology to construct geometric shapes, see the section on uses in technology below.

Artificial bases

Several artificial nucleobases have been synthesized, and successfully incorporated in the eight-base DNA analogue named Hachimoji DNA. Dubbed S, B, P, and Z, these artificial bases are capable of bonding with each other in a predictable way (S–B and P–Z), maintain the double helix structure of DNA, and be transcribed to RNA. Their existence implies that there is nothing special about the four natural nucleobases that evolved on Earth. [86] [87]

Chemical modifications and altered DNA packaging

Cytosin.svg 5-Methylcytosine.svg Thymin.svg
cytosine 5-methylcytosine thymine
Structure of cytosine with and without the 5-methyl group. Deamination converts 5-methylcytosine into thymine.

Base modifications and DNA packaging

The expression of genes is influenced by how the DNA is packaged in chromosomes, in a structure called chromatin. Base modifications can be involved in packaging, with regions that have low or no gene expression usually containing high levels of methylation of cytosine bases. DNA packaging and its influence on gene expression can also occur by covalent modifications of the histone protein core around which DNA is wrapped in the chromatin structure or else by remodeling carried out by chromatin remodeling complexes (see Chromatin remodeling). There is, further, crosstalk between DNA methylation and histone modification, so they can coordinately affect chromatin and gene expression. [88]

For one example, cytosine methylation produces 5-methylcytosine, which is important for X-inactivation of chromosomes. [89] The average level of methylation varies between organisms—the worm Caenorhabditis elegans lacks cytosine methylation, while vertebrates have higher levels, with up to 1% of their DNA containing 5-methylcytosine. [90] Despite the importance of 5-methylcytosine, it can deaminate to leave a thymine base, so methylated cytosines are particularly prone to mutations. [91] Other base modifications include adenine methylation in bacteria, the presence of 5-hydroxymethylcytosine in the brain, [92] and the glycosylation of uracil to produce the "J-base" in kinetoplastids. [93] [94]

Damage

A covalent adduct between a metabolically activated form of benzo[a]pyrene, the major mutagen in tobacco smoke, and DNA Benzopyrene DNA adduct 1JDG.png
A covalent adduct between a metabolically activated form of benzo[a]pyrene, the major mutagen in tobacco smoke, and DNA

DNA can be damaged by many sorts of mutagens, which change the DNA sequence. Mutagens include oxidizing agents, alkylating agents and also high-energy electromagnetic radiation such as ultraviolet light and X-rays. The type of DNA damage produced depends on the type of mutagen. For example, UV light can damage DNA by producing thymine dimers, which are cross-links between pyrimidine bases. [96] On the other hand, oxidants such as free radicals or hydrogen peroxide produce multiple forms of damage, including base modifications, particularly of guanosine, and double-strand breaks. [97] A typical human cell contains about 150,000 bases that have suffered oxidative damage. [98] Of these oxidative lesions, the most dangerous are double-strand breaks, as these are difficult to repair and can produce point mutations, insertions, deletions from the DNA sequence, and chromosomal translocations. [99] These mutations can cause cancer. Because of inherent limits in the DNA repair mechanisms, if humans lived long enough, they would all eventually develop cancer. [100] [101] DNA damages that are naturally occurring, due to normal cellular processes that produce reactive oxygen species, the hydrolytic activities of cellular water, etc., also occur frequently. Although most of these damages are repaired, in any cell some DNA damage may remain despite the action of repair processes. These remaining DNA damages accumulate with age in mammalian postmitotic tissues. This accumulation appears to be an important underlying cause of aging. [102] [103] [104]

Many mutagens fit into the space between two adjacent base pairs, this is called intercalation . Most intercalators are aromatic and planar molecules; examples include ethidium bromide, acridines, daunomycin, and doxorubicin. For an intercalator to fit between base pairs, the bases must separate, distorting the DNA strands by unwinding of the double helix. This inhibits both transcription and DNA replication, causing toxicity and mutations. [105] As a result, DNA intercalators may be carcinogens, and in the case of thalidomide, a teratogen. [106] Others such as benzo[a]pyrene diol epoxide and aflatoxin form DNA adducts that induce errors in replication. [107] Nevertheless, due to their ability to inhibit DNA transcription and replication, other similar toxins are also used in chemotherapy to inhibit rapidly growing cancer cells. [108]

Biological functions

Location of eukaryote nuclear DNA within the chromosomes Eukaryote DNA-en.svg
Location of eukaryote nuclear DNA within the chromosomes

DNA usually occurs as linear chromosomes in eukaryotes, and circular chromosomes in prokaryotes. The set of chromosomes in a cell makes up its genome; the human genome has approximately 3 billion base pairs of DNA arranged into 46 chromosomes. [109] The information carried by DNA is held in the sequence of pieces of DNA called genes. Transmission of genetic information in genes is achieved via complementary base pairing. For example, in transcription, when a cell uses the information in a gene, the DNA sequence is copied into a complementary RNA sequence through the attraction between the DNA and the correct RNA nucleotides. Usually, this RNA copy is then used to make a matching protein sequence in a process called translation, which depends on the same interaction between RNA nucleotides. In alternative fashion, a cell may simply copy its genetic information in a process called DNA replication. The details of these functions are covered in other articles; here the focus is on the interactions between DNA and other molecules that mediate the function of the genome.

Genes and genomes

Genomic DNA is tightly and orderly packed in the process called DNA condensation, to fit the small available volumes of the cell. In eukaryotes, DNA is located in the cell nucleus, with small amounts in mitochondria and chloroplasts. In prokaryotes, the DNA is held within an irregularly shaped body in the cytoplasm called the nucleoid. [110] The genetic information in a genome is held within genes, and the complete set of this information in an organism is called its genotype. A gene is a unit of heredity and is a region of DNA that influences a particular characteristic in an organism. Genes contain an open reading frame that can be transcribed, and regulatory sequences such as promoters and enhancers, which control transcription of the open reading frame.

In many species, only a small fraction of the total sequence of the genome encodes protein. For example, only about 1.5% of the human genome consists of protein-coding exons, with over 50% of human DNA consisting of non-coding repetitive sequences. [111] The reasons for the presence of so much noncoding DNA in eukaryotic genomes and the extraordinary differences in genome size, or C-value , among species, represent a long-standing puzzle known as the "C-value enigma". [112] However, some DNA sequences that do not code protein may still encode functional non-coding RNA molecules, which are involved in the regulation of gene expression. [113]

T7 RNA polymerase (blue) producing an mRNA (green) from a DNA template (orange) T7 RNA polymerase.jpg
T7 RNA polymerase (blue) producing an mRNA (green) from a DNA template (orange)

Some noncoding DNA sequences play structural roles in chromosomes. Telomeres and centromeres typically contain few genes but are important for the function and stability of chromosomes. [79] [115] An abundant form of noncoding DNA in humans are pseudogenes, which are copies of genes that have been disabled by mutation. [116] These sequences are usually just molecular fossils, although they can occasionally serve as raw genetic material for the creation of new genes through the process of gene duplication and divergence. [117]

Transcription and translation

A gene is a sequence of DNA that contains genetic information and can influence the phenotype of an organism. Within a gene, the sequence of bases along a DNA strand defines a messenger RNA sequence, which then defines one or more protein sequences. The relationship between the nucleotide sequences of genes and the amino-acid sequences of proteins is determined by the rules of translation, known collectively as the genetic code. The genetic code consists of three-letter 'words' called codons formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT).

In transcription, the codons of a gene are copied into messenger RNA by RNA polymerase. This RNA copy is then decoded by a ribosome that reads the RNA sequence by base-pairing the messenger RNA to transfer RNA, which carries amino acids. Since there are 4 bases in 3-letter combinations, there are 64 possible codons (43 combinations). These encode the twenty standard amino acids, giving most amino acids more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region; these are the TAA, TGA, and TAG codons.

DNA replication. The double helix is unwound by a helicase and topoisomerase. Next, one DNA polymerase produces the leading strand copy. Another DNA polymerase binds to the lagging strand. This enzyme makes discontinuous segments (called Okazaki fragments) before DNA ligase joins them together. DNA replication en.svg
DNA replication. The double helix is unwound by a helicase and topoisomerase. Next, one DNA polymerase produces the leading strand copy. Another DNA polymerase binds to the lagging strand. This enzyme makes discontinuous segments (called Okazaki fragments) before DNA ligase joins them together.

Replication

Cell division is essential for an organism to grow, but, when a cell divides, it must replicate the DNA in its genome so that the two daughter cells have the same genetic information as their parent. The double-stranded structure of DNA provides a simple mechanism for DNA replication. Here, the two strands are separated and then each strand's complementary DNA sequence is recreated by an enzyme called DNA polymerase. This enzyme makes the complementary strand by finding the correct base through complementary base pairing and bonding it onto the original strand. As DNA polymerases can only extend a DNA strand in a 5′ to 3′ direction, different mechanisms are used to copy the antiparallel strands of the double helix. [118] In this way, the base on the old strand dictates which base appears on the new strand, and the cell ends up with a perfect copy of its DNA.

Extracellular nucleic acids

Naked extracellular DNA (eDNA), most of it released by cell death, is nearly ubiquitous in the environment. Its concentration in soil may be as high as 2 μg/L, and its concentration in natural aquatic environments may be as high at 88 μg/L. [119] Various possible functions have been proposed for eDNA: it may be involved in horizontal gene transfer; [120] it may provide nutrients; [121] and it may act as a buffer to recruit or titrate ions or antibiotics. [122] Extracellular DNA acts as a functional extracellular matrix component in the biofilms of several bacterial species. It may act as a recognition factor to regulate the attachment and dispersal of specific cell types in the biofilm; [123] it may contribute to biofilm formation; [124] and it may contribute to the biofilm's physical strength and resistance to biological stress. [125]

Cell-free fetal DNA is found in the blood of the mother, and can be sequenced to determine a great deal of information about the developing fetus. [126]

Interactions with proteins

All the functions of DNA depend on interactions with proteins. These protein interactions can be non-specific, or the protein can bind specifically to a single DNA sequence. Enzymes can also bind to DNA and of these, the polymerases that copy the DNA base sequence in transcription and DNA replication are particularly important.

DNA-binding proteins

Nucleosome1.png
Interaction of DNA (in orange) with histones (in blue). These proteins' basic amino acids bind to the acidic phosphate groups on DNA.

Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with structural proteins. These proteins organize the DNA into a compact structure called chromatin. In eukaryotes, this structure involves DNA binding to a complex of small basic proteins called histones, while in prokaryotes multiple types of proteins are involved. [127] [128] The histones form a disk-shaped complex called a nucleosome, which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones, making ionic bonds to the acidic sugar-phosphate backbone of the DNA, and are thus largely independent of the base sequence. [129] Chemical modifications of these basic amino acid residues include methylation, phosphorylation, and acetylation. [130] These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factors and changing the rate of transcription. [131] Other non-specific DNA-binding proteins in chromatin include the high-mobility group proteins, which bind to bent or distorted DNA. [132] These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that make up chromosomes. [133]

A distinct group of DNA-binding proteins is the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination, and DNA repair. [134] These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem-loops or being degraded by nucleases.

The lambda repressor helix-turn-helix transcription factor bound to its DNA target Lambda repressor 1LMB.png
The lambda repressor helix-turn-helix transcription factor bound to its DNA target

In contrast, other proteins have evolved to bind to particular DNA sequences. The most intensively studied of these are the various transcription factors, which are proteins that regulate transcription. Each transcription factor binds to one particular set of DNA sequences and activates or inhibits the transcription of genes that have these sequences close to their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription. [136] Alternatively, transcription factors can bind enzymes that modify the histones at the promoter. This changes the accessibility of the DNA template to the polymerase. [137]

As these DNA targets can occur throughout an organism's genome, changes in the activity of one type of transcription factor can affect thousands of genes. [138] Consequently, these proteins are often the targets of the signal transduction processes that control responses to environmental changes or cellular differentiation and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to "read" the DNA sequence. Most of these base-interactions are made in the major groove, where the bases are most accessible. [47]

The restriction enzyme EcoRV (green) in a complex with its substrate DNA EcoRV 1RVA.png
The restriction enzyme EcoRV (green) in a complex with its substrate DNA

DNA-modifying enzymes

Nucleases and ligases

Nucleases are enzymes that cut DNA strands by catalyzing the hydrolysis of the phosphodiester bonds. Nucleases that hydrolyse nucleotides from the ends of DNA strands are called exonucleases, while endonucleases cut within strands. The most frequently used nucleases in molecular biology are the restriction endonucleases, which cut DNA at specific sequences. For instance, the EcoRV enzyme shown to the left recognizes the 6-base sequence 5′-GATATC-3′ and makes a cut at the horizontal line. In nature, these enzymes protect bacteria against phage infection by digesting the phage DNA when it enters the bacterial cell, acting as part of the restriction modification system. [140] In technology, these sequence-specific nucleases are used in molecular cloning and DNA fingerprinting.

Enzymes called DNA ligases can rejoin cut or broken DNA strands. [141] Ligases are particularly important in lagging strand DNA replication, as they join together the short segments of DNA produced at the replication fork into a complete copy of the DNA template. They are also used in DNA repair and genetic recombination. [141]

Topoisomerases and helicases

Topoisomerases are enzymes with both nuclease and ligase activity. These proteins change the amount of supercoiling in DNA. Some of these enzymes work by cutting the DNA helix and allowing one section to rotate, thereby reducing its level of supercoiling; the enzyme then seals the DNA break. [60] Other types of these enzymes are capable of cutting one DNA helix and then passing a second strand of DNA through this break, before rejoining the helix. [142] Topoisomerases are required for many processes involving DNA, such as DNA replication and transcription. [61]

Helicases are proteins that are a type of molecular motor. They use the chemical energy in nucleoside triphosphates, predominantly adenosine triphosphate (ATP), to break hydrogen bonds between bases and unwind the DNA double helix into single strands. [143] These enzymes are essential for most processes where enzymes need to access the DNA bases.

Polymerases

Polymerases are enzymes that synthesize polynucleotide chains from nucleoside triphosphates. The sequence of their products is created based on existing polynucleotide chains—which are called templates. These enzymes function by repeatedly adding a nucleotide to the 3′ hydroxyl group at the end of the growing polynucleotide chain. As a consequence, all polymerases work in a 5′ to 3′ direction. [144] In the active site of these enzymes, the incoming nucleoside triphosphate base-pairs to the template: this allows polymerases to accurately synthesize the complementary strand of their template. Polymerases are classified according to the type of template that they use.

In DNA replication, DNA-dependent DNA polymerases make copies of DNA polynucleotide chains. To preserve biological information, it is essential that the sequence of bases in each copy are precisely complementary to the sequence of bases in the template strand. Many DNA polymerases have a proofreading activity. Here, the polymerase recognizes the occasional mistakes in the synthesis reaction by the lack of base pairing between the mismatched nucleotides. If a mismatch is detected, a 3′ to 5′ exonuclease activity is activated and the incorrect base removed. [145] In most organisms, DNA polymerases function in a large complex called the replisome that contains multiple accessory subunits, such as the DNA clamp or helicases. [146]

RNA-dependent DNA polymerases are a specialized class of polymerases that copy the sequence of an RNA strand into DNA. They include reverse transcriptase, which is a viral enzyme involved in the infection of cells by retroviruses, and telomerase, which is required for the replication of telomeres. [78] [147] For example, HIV reverse transcriptase is an enzyme for AIDS virus replication. [147] Telomerase is an unusual polymerase because it contains its own RNA template as part of its structure. It synthesizes telomeres at the ends of chromosomes. Telomeres prevent fusion of the ends of neighboring chromosomes and protect chromosome ends from damage. [79]

Transcription is carried out by a DNA-dependent RNA polymerase that copies the sequence of a DNA strand into RNA. To begin transcribing a gene, the RNA polymerase binds to a sequence of DNA called a promoter and separates the DNA strands. It then copies the gene sequence into a messenger RNA transcript until it reaches a region of DNA called the terminator, where it halts and detaches from the DNA. As with human DNA-dependent DNA polymerases, RNA polymerase II, the enzyme that transcribes most of the genes in the human genome, operates as part of a large protein complex with multiple regulatory and accessory subunits. [148]

Genetic recombination

Holliday Junction.svg
Holliday junction coloured.png
Structure of the Holliday junction intermediate in genetic recombination. The four separate DNA strands are coloured red, blue, green and yellow. [149]
Recombination involves the breaking and rejoining of two chromosomes (M and F) to produce two rearranged chromosomes (C1 and C2). Chromosomal Recombination.svg
Recombination involves the breaking and rejoining of two chromosomes (M and F) to produce two rearranged chromosomes (C1 and C2).

A DNA helix usually does not interact with other segments of DNA, and in human cells, the different chromosomes even occupy separate areas in the nucleus called "chromosome territories". [150] This physical separation of different chromosomes is important for the ability of DNA to function as a stable repository for information, as one of the few times chromosomes interact is in chromosomal crossover which occurs during sexual reproduction, when genetic recombination occurs. Chromosomal crossover is when two DNA helices break, swap a section and then rejoin.

Recombination allows chromosomes to exchange genetic information and produces new combinations of genes, which increases the efficiency of natural selection and can be important in the rapid evolution of new proteins. [151] Genetic recombination can also be involved in DNA repair, particularly in the cell's response to double-strand breaks. [152]

The most common form of chromosomal crossover is homologous recombination, where the two chromosomes involved share very similar sequences. Non-homologous recombination can be damaging to cells, as it can produce chromosomal translocations and genetic abnormalities. The recombination reaction is catalyzed by enzymes known as recombinases, such as RAD51. [153] The first step in recombination is a double-stranded break caused by either an endonuclease or damage to the DNA. [154] A series of steps catalyzed in part by the recombinase then leads to joining of the two helices by at least one Holliday junction, in which a segment of a single strand in each helix is annealed to the complementary strand in the other helix. The Holliday junction is a tetrahedral junction structure that can be moved along the pair of chromosomes, swapping one strand for another. The recombination reaction is then halted by cleavage of the junction and re-ligation of the released DNA. [155] Only strands of like polarity exchange DNA during recombination. There are two types of cleavage: east-west cleavage and north-south cleavage. The north-south cleavage nicks both strands of DNA, while the east-west cleavage has one strand of DNA intact. The formation of a Holliday junction during recombination makes it possible for genetic diversity, genes to exchange on chromosomes, and expression of wild-type viral genomes.

Evolution

DNA contains the genetic information that allows all forms of life to function, grow and reproduce. However, it is unclear how long in the 4-billion-year history of life DNA has performed this function, as it has been proposed that the earliest forms of life may have used RNA as their genetic material. [156] [157] RNA may have acted as the central part of early cell metabolism as it can both transmit genetic information and carry out catalysis as part of ribozymes. [158] This ancient RNA world where nucleic acid would have been used for both catalysis and genetics may have influenced the evolution of the current genetic code based on four nucleotide bases. This would occur, since the number of different bases in such an organism is a trade-off between a small number of bases increasing replication accuracy and a large number of bases increasing the catalytic efficiency of ribozymes. [159] However, there is no direct evidence of ancient genetic systems, as recovery of DNA from most fossils is impossible because DNA survives in the environment for less than one million years, and slowly degrades into short fragments in solution. [160] Claims for older DNA have been made, most notably a report of the isolation of a viable bacterium from a salt crystal 250 million years old, [161] but these claims are controversial. [162] [163]

Building blocks of DNA (adenine, guanine, and related organic molecules) may have been formed extraterrestrially in outer space. [164] [165] [166] Complex DNA and RNA organic compounds of life, including uracil, cytosine, and thymine, have also been formed in the laboratory under conditions mimicking those found in outer space, using starting chemicals, such as pyrimidine, found in meteorites. Pyrimidine, like polycyclic aromatic hydrocarbons (PAHs), the most carbon-rich chemical found in the universe, may have been formed in red giants or in interstellar cosmic dust and gas clouds. [167]

Uses in technology

Genetic engineering

Methods have been developed to purify DNA from organisms, such as phenol-chloroform extraction, and to manipulate it in the laboratory, such as restriction digests and the polymerase chain reaction. Modern biology and biochemistry make intensive use of these techniques in recombinant DNA technology. Recombinant DNA is a man-made DNA sequence that has been assembled from other DNA sequences. They can be transformed into organisms in the form of plasmids or in the appropriate format, by using a viral vector. [168] The genetically modified organisms produced can be used to produce products such as recombinant proteins, used in medical research, [169] or be grown in agriculture. [170] [171]

DNA profiling

Forensic scientists can use DNA in blood, semen, skin, saliva or hair found at a crime scene to identify a matching DNA of an individual, such as a perpetrator. [172] This process is formally termed DNA profiling, also called DNA fingerprinting. In DNA profiling, the lengths of variable sections of repetitive DNA, such as short tandem repeats and minisatellites, are compared between people. This method is usually an extremely reliable technique for identifying a matching DNA. [173] However, identification can be complicated if the scene is contaminated with DNA from several people. [174] DNA profiling was developed in 1984 by British geneticist Sir Alec Jeffreys, [175] and first used in forensic science to convict Colin Pitchfork in the 1988 Enderby murders case. [176]

The development of forensic science and the ability to now obtain genetic matching on minute samples of blood, skin, saliva, or hair has led to re-examining many cases. Evidence can now be uncovered that was scientifically impossible at the time of the original examination. Combined with the removal of the double jeopardy law in some places, this can allow cases to be reopened where prior trials have failed to produce sufficient evidence to convince a jury. People charged with serious crimes may be required to provide a sample of DNA for matching purposes. The most obvious defense to DNA matches obtained forensically is to claim that cross-contamination of evidence has occurred. This has resulted in meticulous strict handling procedures with new cases of serious crime.

DNA profiling is also used successfully to positively identify victims of mass casualty incidents, [177] bodies or body parts in serious accidents, and individual victims in mass war graves, via matching to family members.

DNA profiling is also used in DNA paternity testing to determine if someone is the biological parent or grandparent of a child with the probability of parentage is typically 99.99% when the alleged parent is biologically related to the child. Normal DNA sequencing methods happen after birth, but there are new methods to test paternity while a mother is still pregnant. [178]

DNA enzymes or catalytic DNA

Deoxyribozymes, also called DNAzymes or catalytic DNA, were first discovered in 1994. [179] They are mostly single stranded DNA sequences isolated from a large pool of random DNA sequences through a combinatorial approach called in vitro selection or systematic evolution of ligands by exponential enrichment (SELEX). DNAzymes catalyze variety of chemical reactions including RNA-DNA cleavage, RNA-DNA ligation, amino acids phosphorylation-dephosphorylation, carbon-carbon bond formation, and etc. DNAzymes can enhance catalytic rate of chemical reactions up to 100,000,000,000-fold over the uncatalyzed reaction. [180] The most extensively studied class of DNAzymes is RNA-cleaving types which have been used to detect different metal ions and designing therapeutic agents. Several metal-specific DNAzymes have been reported including the GR-5 DNAzyme (lead-specific), [179] the CA1-3 DNAzymes (copper-specific), [181] the 39E DNAzyme (uranyl-specific) and the NaA43 DNAzyme (sodium-specific). [182] The NaA43 DNAzyme, which is reported to be more than 10,000-fold selective for sodium over other metal ions, was used to make a real-time sodium sensor in cells.

Bioinformatics

Bioinformatics involves the development of techniques to store, data mine, search and manipulate biological data, including DNA nucleic acid sequence data. These have led to widely applied advances in computer science, especially string searching algorithms, machine learning, and database theory. [183] String searching or matching algorithms, which find an occurrence of a sequence of letters inside a larger sequence of letters, were developed to search for specific sequences of nucleotides. [184] The DNA sequence may be aligned with other DNA sequences to identify homologous sequences and locate the specific mutations that make them distinct. These techniques, especially multiple sequence alignment, are used in studying phylogenetic relationships and protein function. [185] Data sets representing entire genomes' worth of DNA sequences, such as those produced by the Human Genome Project, are difficult to use without the annotations that identify the locations of genes and regulatory elements on each chromosome. Regions of DNA sequence that have the characteristic patterns associated with protein- or RNA-coding genes can be identified by gene finding algorithms, which allow researchers to predict the presence of particular gene products and their possible functions in an organism even before they have been isolated experimentally. [186] Entire genomes may also be compared, which can shed light on the evolutionary history of particular organism and permit the examination of complex evolutionary events.

DNA nanotechnology

The DNA structure at left (schematic shown) will self-assemble into the structure visualized by atomic force microscopy at right. DNA nanotechnology is the field that seeks to design nanoscale structures using the molecular recognition properties of DNA molecules. Image from Strong, 2004. DNA nanostructures.png
The DNA structure at left (schematic shown) will self-assemble into the structure visualized by atomic force microscopy at right. DNA nanotechnology is the field that seeks to design nanoscale structures using the molecular recognition properties of DNA molecules. Image from Strong, 2004.

DNA nanotechnology uses the unique molecular recognition properties of DNA and other nucleic acids to create self-assembling branched DNA complexes with useful properties. [187] DNA is thus used as a structural material rather than as a carrier of biological information. This has led to the creation of two-dimensional periodic lattices (both tile-based and using the DNA origami method) and three-dimensional structures in the shapes of polyhedra. [188] Nanomechanical devices and algorithmic self-assembly have also been demonstrated, [189] and these DNA structures have been used to template the arrangement of other molecules such as gold nanoparticles and streptavidin proteins. [190]

History and anthropology

Because DNA collects mutations over time, which are then inherited, it contains historical information, and, by comparing DNA sequences, geneticists can infer the evolutionary history of organisms, their phylogeny. [191] This field of phylogenetics is a powerful tool in evolutionary biology. If DNA sequences within a species are compared, population geneticists can learn the history of particular populations. This can be used in studies ranging from ecological genetics to anthropology.

Information storage

DNA as a storage device for information has enormous potential since it has much higher storage density compared to electronic devices. However high costs, extremely slow read and write times (memory latency), and insufficient reliability has prevented its practical use. [192] [193]

History

James Watson and Francis Crick (right), co-originators of the double-helix model, with Maclyn McCarty (left) Maclyn McCarty with Francis Crick and James D Watson - 10.1371 journal.pbio.0030341.g001-O.jpg
James Watson and Francis Crick (right), co-originators of the double-helix model, with Maclyn McCarty (left)
Pencil sketch of the DNA double helix by Francis Crick in 1953 Pencil sketch of the DNA double helix by Francis Crick Wellcome L0051225.jpg
Pencil sketch of the DNA double helix by Francis Crick in 1953

DNA was first isolated by the Swiss physician Friedrich Miescher who, in 1869, discovered a microscopic substance in the pus of discarded surgical bandages. As it resided in the nuclei of cells, he called it "nuclein". [194] [195] In 1878, Albrecht Kossel isolated the non-protein component of "nuclein", nucleic acid, and later isolated its five primary nucleobases. [196] [197]

In 1909, Phoebus Levene identified the base, sugar, and phosphate nucleotide unit of the RNA (then named "yeast nucleic acid"). [198] [199] [200] In 1929, Levene identified deoxyribose sugar in "thymus nucleic acid" (DNA). [201] Levene suggested that DNA consisted of a string of four nucleotide units linked together through the phosphate groups ("tetranucleotide hypothesis"). Levene thought the chain was short and the bases repeated in a fixed order. In 1927, Nikolai Koltsov proposed that inherited traits would be inherited via a "giant hereditary molecule" made up of "two mirror strands that would replicate in a semi-conservative fashion using each strand as a template". [202] [203] In 1928, Frederick Griffith in his experiment discovered that traits of the "smooth" form of Pneumococcus could be transferred to the "rough" form of the same bacteria by mixing killed "smooth" bacteria with the live "rough" form. [204] [205] This system provided the first clear suggestion that DNA carries genetic information.

In 1933, while studying virgin sea urchin eggs, Jean Brachet suggested that DNA is found in the cell nucleus and that RNA is present exclusively in the cytoplasm. At the time, "yeast nucleic acid" (RNA) was thought to occur only in plants, while "thymus nucleic acid" (DNA) only in animals. The latter was thought to be a tetramer, with the function of buffering cellular pH. [206] [207]

In 1937, William Astbury produced the first X-ray diffraction patterns that showed that DNA had a regular structure. [208]

In 1943, Oswald Avery, along with co-workers Colin MacLeod and Maclyn McCarty, identified DNA as the transforming principle, supporting Griffith's suggestion (Avery–MacLeod–McCarty experiment). [209] DNA's role in heredity was confirmed in 1952 when Alfred Hershey and Martha Chase in the Hershey–Chase experiment showed that DNA is the genetic material of the enterobacteria phage T2. [210]

A blue plaque outside The Eagle pub commemorating Crick and Watson TheEaglePub-Cambridge-BluePlaque.jpg
A blue plaque outside The Eagle pub commemorating Crick and Watson

Late in 1951, Francis Crick started working with James Watson at the Cavendish Laboratory within the University of Cambridge. In 1953, Watson and Crick suggested what is now accepted as the first correct double-helix model of DNA structure in the journal Nature. [9] Their double-helix, molecular model of DNA was then based on one X-ray diffraction image (labeled as "Photo 51") [211] taken by Rosalind Franklin and Raymond Gosling in May 1952, and the information that the DNA bases are paired. On 28 February 1953 Crick interrupted patrons' lunchtime at The Eagle pub in Cambridge to announce that he and Watson had "discovered the secret of life". [212]

Months earlier, in February 1953, Linus Pauling and Robert Corey proposed a model for nucleic acids containing three intertwined chains, with the phosphates near the axis, and the bases on the outside. [213] Experimental evidence supporting the Watson and Crick model was published in a series of five articles in the same issue of Nature. [214] Of these, Franklin and Gosling's paper was the first publication of their own X-ray diffraction data and original analysis method that partly supported the Watson and Crick model; [64] [215] this issue also contained an article on DNA structure by Maurice Wilkins and two of his colleagues, whose analysis and in vivo B-DNA X-ray patterns also supported the presence in vivo of the double-helical DNA configurations as proposed by Crick and Watson for their double-helix molecular model of DNA in the prior two pages of Nature. [65] In 1962, after Franklin's death, Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine. [216] Nobel Prizes are awarded only to living recipients. A debate continues about who should receive credit for the discovery. [217]

In an influential presentation in 1957, Crick laid out the central dogma of molecular biology, which foretold the relationship between DNA, RNA, and proteins, and articulated the "adaptor hypothesis". [218] Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the Meselson–Stahl experiment. [219] Further work by Crick and co-workers showed that the genetic code was based on non-overlapping triplets of bases, called codons, allowing Har Gobind Khorana, Robert W. Holley, and Marshall Warren Nirenberg to decipher the genetic code. [220] These findings represent the birth of molecular biology. [221]

See also

Related Research Articles

Base pair unit consisting of two nucleobases bound to each other by hydrogen bonds: either adenine–thymine or guanine–cytosine in natural DNA (additional types occur in RNA)

A base pair (bp) is a unit consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA and RNA. Dictated by specific hydrogen bonding patterns, Watson–Crick base pairs allow the DNA helix to maintain a regular helical structure that is subtly dependent on its nucleotide sequence. The complementary nature of this based-paired structure provides a redundant copy of the genetic information encoded within each strand of DNA. The regular structure and data redundancy provided by the DNA double helix make DNA well suited to the storage of genetic information, while base-pairing between DNA and incoming nucleotides provides the mechanism through which DNA polymerase replicates DNA and RNA polymerase transcribes DNA into RNA. Many DNA-binding proteins can recognize specific base-pairing patterns that identify particular regulatory regions of genes.

RNA family of large biological molecules

Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and DNA are nucleic acids, and, along with lipids, proteins and carbohydrates, constitute the four major macromolecules essential for all known forms of life. Like DNA, RNA is assembled as a chain of nucleotides, but unlike DNA it is more often found in nature as a single-strand folded onto itself, rather than a paired double-strand. Cellular organisms use messenger RNA (mRNA) to convey genetic information that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome.

RNA world hypothetical phase of the evolutionary history of life on Earth, in which self-replicating RNA molecules proliferated before the evolution of DNA and proteins

The RNA world is a hypothetical stage in the evolutionary history of life on Earth, in which self-replicating RNA molecules proliferated before the evolution of DNA and proteins. The term also refers to the hypothesis that posits the existence of this stage.

Molecular evolution The process of change in the sequence composition of cellular molecules across generations

Molecular evolution is the process of change in the sequence composition of cellular molecules such as DNA, RNA, and proteins across generations. The field of molecular evolution uses principles of evolutionary biology and population genetics to explain patterns in these changes. Major topics in molecular evolution concern the rates and impacts of single nucleotide changes, neutral evolution vs. natural selection, origins of new genes, the genetic nature of complex traits, the genetic basis of speciation, evolution of development, and ways that evolutionary forces influence genomic and phenotypic changes.

DNA polymerase Enzyme that synthesizes DNA from a DNA template

DNA polymerase is an enzyme that synthesizes DNA molecules from deoxyribonucleotides, the building blocks of DNA. These enzymes are essential for DNA replication and usually work in pairs to create two identical DNA strands from a single original DNA molecule. During this process, DNA polymerase "reads" the existing DNA strands to create two new strands that match the existing ones.

Nucleic acid sequence A succession of nucleotides in a nucleic acid

A nucleic acid sequence is a succession of letters that indicate the order of nucleotides forming alleles within a DNA or RNA (GACU) molecule. By convention, sequences are usually presented from the 5' end to the 3' end. For DNA, the sense strand is used. Because nucleic acids are normally linear (unbranched) polymers, specifying the sequence is equivalent to defining the covalent structure of the entire molecule. For this reason, the nucleic acid sequence is also termed the primary structure.

Reading frame

In molecular biology, a reading frame is a way of dividing the sequence of nucleotides in a nucleic acid molecule into a set of consecutive, non-overlapping triplets. Where these triplets equate to amino acids or stop signals during translation, they are called codons.

DNA-binding protein proteins that have DNA-binding domains and thus have a specific or general affinity for single- or double-stranded DNA

DNA-binding proteins are proteins that have DNA-binding domains and thus have a specific or general affinity for single- or double-stranded DNA. Sequence-specific DNA-binding proteins generally interact with the major groove of B-DNA, because it exposes more functional groups that identify a base pair. However, there are some known minor groove DNA-binding ligands such as netropsin, distamycin, Hoechst 33258, pentamidine, DAPI and others.

DNA sequencing process of determining the nucleic acid sequence – the order of nucleotides in DNA

DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, guanine, cytosine, and thymine. The advent of rapid DNA sequencing methods has greatly accelerated biological and medical research and discovery.

Nuclear DNA(nDNA), or nuclear deoxyribonucleic acid, is the DNA contained within each cell nucleus of a eukaryotic organism. Nuclear DNA encodes for the majority of the genome in eukaryotes, with mitochondrial DNA and plastid DNA coding for the rest. Nuclear DNA adheres to Mendelian inheritance, with information coming from two parents, one male and one female, rather than matrilineally as in mitochondrial DNA.

In molecular biology and genetics, the sense of nucleic acid molecules is the nature of their roles and their complementary molecules' nucleic acid units' roles in specifying amino acids. Depending on the context within molecular biology, sense may have slightly different meanings.

Palindromic sequence nucleic acid sequence on double-stranded DNA or RNA

A palindromic sequence is a nucleic acid sequence on double-stranded DNA or RNA wherein reading 5' (five-prime) to 3' forward on one strand matches the sequence reading 5' to 3' on the complementary strand with which it forms a double helix. This definition of palindrome thus depends on complementary strands being palindromic of each other.

Nucleic acid structure organization of DNA and RNA molecules at different scales

Nucleic acid structure refers to the structure of nucleic acids such as DNA and RNA. Chemically speaking, DNA and RNA are very similar. Nucleic acid structure is often divided into four different levels: primary, secondary, tertiary and quaternary.

Nucleic acid secondary structure basepairing interactions within a single nucleic acid polymer or between two polymers, list of bases which are paired in a nucleic acid molecule

Nucleic acid secondary structure is the basepairing interactions within a single nucleic acid polymer or between two polymers. It can be represented as a list of bases which are paired in a nucleic acid molecule. The secondary structures of biological DNA's and RNA's tend to be different: biological DNA mostly exists as fully base paired double helices, while biological RNA is single stranded and often forms complex and intricate base-pairing interactions due to its increased ability to form hydrogen bonds stemming from the extra hydroxyl group in the ribose sugar.

Numerous key discoveries in biology have emerged from studies of RNA, including seminal work in the fields of biochemistry, genetics, microbiology, molecular biology, molecular evolution and structural biology. As of 2010, 30 scientists have been awarded Nobel Prizes for experimental work that includes studies of RNA. Specific discoveries of high biological significance are discussed in this article.

Complementarity (molecular biology) describes a relationship between two structures each following the lock-and-key principle

In molecular biology, complementarity describes a relationship between two structures each following the lock-and-key principle. In nature complementarity is the base principle of DNA replication and transcription as it is a property shared between two DNA or RNA sequences, such that when they are aligned antiparallel to each other, the nucleotide bases at each position in the sequences will be complementary, much like looking in the mirror and seeing the reverse of things. This complementary base pairing allows cells to copy information from one generation to another and even find and repair damage to the information stored in the sequences.

References

  1. "Deoxyribonucleic acid". Merriam-Webster Dictionary .
  2. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2014). Molecular Biology of the Cell (6th ed.). Garland. p. Chapter 4: DNA, Chromosomes and Genomes. ISBN   978-0-8153-4432-2. Archived from the original on 14 July 2014.
  3. Purcell A. "DNA". Basic Biology. Archived from the original on 5 January 2017.
  4. Russell P (2001). iGenetics. New York: Benjamin Cummings. ISBN   0-8053-4553-1.
  5. Mashaghi A, Katan A (2013). "A physicist's view of DNA". De Physicus. 24e (3): 59–61. arXiv: 1311.2545v1 . Bibcode:2013arXiv1311.2545M.
  6. Saenger W (1984). Principles of Nucleic Acid Structure. New York: Springer-Verlag. ISBN   0-387-90762-9.
  7. 1 2 Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Peter W (2002). Molecular Biology of the Cell (Fourth ed.). New York and London: Garland Science. ISBN   0-8153-3218-1. OCLC   145080076. Archived from the original on 1 November 2016.
  8. Irobalieva RN, Fogg JM, Catanese DJ, Catanese DJ, Sutthibutpong T, Chen M, Barker AK, Ludtke SJ, Harris SA, Schmid MF, Chiu W, Zechiedrich L (October 2015). "Structural diversity of supercoiled DNA". Nature Communications. 6: 8440. Bibcode:2015NatCo...6E8440I. doi:10.1038/ncomms9440. PMC   4608029 . PMID   26455586.
  9. 1 2 3 4 Watson JD, Crick FH (April 1953). "Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid" (PDF). Nature. 171 (4356): 737–38. Bibcode:1953Natur.171..737W. doi:10.1038/171737a0. PMID   13054692. Archived (PDF) from the original on 4 February 2007.
  10. Mandelkern M, Elias JG, Eden D, Crothers DM (October 1981). "The dimensions of DNA in solution". Journal of Molecular Biology. 152 (1): 153–61. doi:10.1016/0022-2836(81)90099-1. PMID   7338906.
  11. Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, et al. (May 2006). "The DNA sequence and biological annotation of human chromosome 1". Nature. 441 (7091): 315–21. Bibcode:2006Natur.441..315G. doi:10.1038/nature04727. PMID   16710414.
  12. 1 2 3 Berg J, Tymoczko J, Stryer L (2002). Biochemistry. W.H. Freeman and Company. ISBN   0-7167-4955-6.
  13. IUPAC-IUB Commission on Biochemical Nomenclature (CBN) (December 1970). "Abbreviations and Symbols for Nucleic Acids, Polynucleotides and their Constituents. Recommendations 1970". The Biochemical Journal. 120 (3): 449–54. doi:10.1042/bj1200449. PMC   1179624 . PMID   5499957. Archived from the original on 5 February 2007.
  14. 1 2 Ghosh A, Bansal M (April 2003). "A glossary of DNA structures from A to Z". Acta Crystallographica Section D. 59 (Pt 4): 620–26. doi:10.1107/S0907444903003251. PMID   12657780.
  15. Created from PDB 1D65
  16. Yakovchuk P, Protozanova E, Frank-Kamenetskii MD (2006). "Base-stacking and base-pairing contributions into thermal stability of the DNA double helix". Nucleic Acids Research. 34 (2): 564–74. doi:10.1093/nar/gkj454. PMC   1360284 . PMID   16449200.
  17. Tropp BE (2012). Molecular Biology (4th ed.). Sudbury, Mass.: Jones and Barlett Learning. ISBN   978-0-7637-8663-2.
  18. Carr S (1953). "Watson-Crick Structure of DNA". Memorial University of Newfoundland. Archived from the original on 19 July 2016. Retrieved 13 July 2016.
  19. Verma S, Eckstein F (1998). "Modified oligonucleotides: synthesis and strategy for users". Annual Review of Biochemistry. 67: 99–134. doi:10.1146/annurev.biochem.67.1.99. PMID   9759484.
  20. Kiljunen S, Hakala K, Pinta E, Huttunen S, Pluta P, Gador A, Lönnberg H, Skurnik M (December 2005). "Yersiniophage phiR1-37 is a tailed bacteriophage having a 270 kb DNA genome with thymidine replaced by deoxyuridine". Microbiology. 151 (Pt 12): 4093–102. doi:10.1099/mic.0.28265-0. PMID   16339954.
  21. Uchiyama J, Takemura-Uchiyama I, Sakaguchi Y, Gamoh K, Kato S, Daibata M, Ujihara T, Misawa N, Matsuzaki S (September 2014). "Intragenus generalized transduction in Staphylococcus spp. by a novel giant phage". The ISME Journal. 8 (9): 1949–52. doi:10.1038/ismej.2014.29. PMC   4139722 . PMID   24599069.
  22. Molnár P, Marton L, Izrael R, Pálinkás HL, Vértessy BG (2018) Uracil moieties in Plasmodium falciparum genomic DNA. FEBS Open Bio 8(11):1763–1772
  23. Casella E, Markewych O, Dosmar M, Heman W (1978) Production and expression of dTMP-enriched DNA of bacteriophage SP15. J Virology 28 (3) 753–66
  24. Simpson L (March 1998). "A base called J". Proceedings of the National Academy of Sciences of the United States of America. 95 (5): 2037–38. Bibcode:1998PNAS...95.2037S. doi:10.1073/pnas.95.5.2037. PMC   33841 . PMID   9482833.
  25. Borst P, Sabatini R (2008). "Base J: discovery, biosynthesis, and possible functions". Annual Review of Microbiology. 62: 235–51. doi:10.1146/annurev.micro.62.081307.162750. PMID   18729733.
  26. Cross M, Kieft R, Sabatini R, Wilm M, de Kort M, van der Marel GA, van Boom JH, van Leeuwen F, Borst P (November 1999). "The modified base J is the target for a novel DNA-binding protein in kinetoplastid protozoans". The EMBO Journal. 18 (22): 6573–81. doi:10.1093/emboj/18.22.6573. PMC   1171720 . PMID   10562569.
  27. DiPaolo C, Kieft R, Cross M, Sabatini R (February 2005). "Regulation of trypanosome DNA glycosylation by a SWI2/SNF2-like protein". Molecular Cell. 17 (3): 441–51. doi:10.1016/j.molcel.2004.12.022. PMID   15694344.
  28. Vainio S, Genest PA, ter Riet B, van Luenen H, Borst P (April 2009). "Evidence that J-binding protein 2 is a thymidine hydroxylase catalyzing the first step in the biosynthesis of DNA base J". Molecular and Biochemical Parasitology. 164 (2): 157–61. doi:10.1016/j.molbiopara.2008.12.001. PMID   19114062.
  29. Iyer LM, Tahiliani M, Rao A, Aravind L (June 2009). "Prediction of novel families of enzymes involved in oxidative and other complex modifications of bases in nucleic acids". Cell Cycle. 8 (11): 1698–710. doi:10.4161/cc.8.11.8580. PMC   2995806 . PMID   19411852.
  30. van Luenen HG, Farris C, Jan S, Genest PA, Tripathi P, Velds A, Kerkhoven RM, Nieuwland M, Haydock A, Ramasamy G, Vainio S, Heidebrecht T, Perrakis A, Pagie L, van Steensel B, Myler PJ, Borst P (August 2012). "Glucosylated hydroxymethyluracil, DNA base J, prevents transcriptional readthrough in Leishmania". Cell. 150 (5): 909–21. doi:10.1016/j.cell.2012.07.030. PMC   3684241 . PMID   22939620.
  31. Hazelbaker DZ, Buratowski S (November 2012). "Transcription: base J blocks the way". Current Biology. 22 (22): R960–2. doi:10.1016/j.cub.2012.10.010. PMC   3648658 . PMID   23174300.
  32. Khudyakov IY, Kirnos MD, Alexandrushkina NI, Vanyushin BF (1978). "Cyanophage S-2L contains DNA with 2,6-diaminopurine substituted for adenine". Virology. 88 (1): 8–18. doi:10.1016/0042-6822(78)90104-6. PMID   676082.
  33. Thiaville JJ, Kellner SM, Yuan Y, Hutinet G, Thiaville PC, Jumpathong W, Mohapatra S, Brochier-Armanet C, Letarov AV, Hillebrand R, Malik CK, Rizzo CJ, Dedon PC, de Crécy-Lagard V (2016). "Novel genomic island modifies DNA with 7-deazaguanine derivatives". Proceedings of the National Academy of Sciences of the United States of America. 113 (11): E1452–59. Bibcode:2016PNAS..113E1452T. doi:10.1073/pnas.1518570113. PMC   4801273 . PMID   26929322.
  34. Johnson TB, Coghill RD (1925). "Pyrimidines. CIII. The discovery of 5-methylcytosine in tuberculinic acid, the nucleic acid of the tubercle bacillus". Journal of the American Chemical Society. 47: 2838–44. doi:10.1021/ja01688a030.
  35. Wyatt GR, Cohen SS (1953). "The bases of the nucleic acids of some bacterial and animal viruses: the occurrence of 5-hydroxymethylcytosine". The Biochemical Journal. 55 (5): 774–82. doi:10.1042/bj0550774. PMC   1269533 . PMID   13115372.
  36. Kuo TT, Huang TC, Teng MH (1968). "5-Methylcytosine replacing cytosine in the deoxyribonucleic acid of a bacteriophage for Xanthomonas oryzae". Journal of Molecular Biology. 34 (2): 373–75. doi:10.1016/0022-2836(68)90263-5. PMID   5760463.
  37. Vogelsang-Wenke H, Oesterhelt D (March 1988). "Isolation of a halobacterial phage with a fully cytosine-methylated genome". MGG Molecular & General Genetics. 211 (3): 407–14. doi:10.1007/BF00425693.
  38. Dunn DB, Smith JD (1955). "Occurrence of a new base in the deoxyribonucleic acid of a strain of Bacterium coli". Nature. 175 (4451): 336–37. doi:10.1038/175336a0. PMID   13235889.
  39. Allet B, Bukhari AI (1975). "Analysis of bacteriophage mu and lambda-mu hybrid DNAs by specific endonucleases". Journal of Molecular Biology. 92 (4): 529–40. doi:10.1016/0022-2836(75)90307-1. PMID   1097703.
  40. Nikolskaya II, Lopatina NG, Debov SS (1976). "Methylated guanine derivative as a minor base in the DNA of phage DDVI Shigella disenteriae". Biochimica et Biophysica Acta. 435 (2): 206–10. doi:10.1016/0005-2787(76)90251-3. PMID   779843.
  41. Janulaitis A, Klimasauskas S, Petrusyte M, Butkus V (1983). "Cytosine modification in DNA by BcnI methylase yields N4-methylcytosine". FEBS Letters. 161 (1): 131–34. doi:10.1016/0014-5793(83)80745-5. PMID   6884523.
  42. Swinton D, Hattman S, Benzinger R, Buchanan-Wollaston V, Beringer J (1985). "Replacement of the deoxycytidine residues in Rhizobium bacteriophage RL38JI DNA". FEBS Letters. 184 (2): 294–98. doi:10.1016/0014-5793(85)80625-6. PMID   2987032.
  43. Maltman KL, Neuhard J, Warren RA (1981). "5-[(Hydroxymethyl)-O-pyrophosphoryl]uracil, an intermediate in the biosynthesis of alpha-putrescinylthymine in deoxyribonucleic acid of bacteriophage phi W-14". Biochemistry. 20 (12): 3586–91. doi:10.1021/bi00515a043. PMID   7260058.
  44. Carell T, Kurz MQ, Müller M, Rossa M, Spada F (2017). "Non-canonical bases in the genome: The regulatory information layer in DNA". Angewandte Chemie (International Ed. in English). 57: 4296–4312. doi:10.1002/anie.201708228. PMID   28941008.
  45. Shu X, Liu M, Lu Z, Zhu C, Meng H, Huang S, Zhang X, Yi C (2018) Genome-wide mapping reveals that deoxyuridine is enriched in the human centromeric DNA. Nat Chem Biol doi : 10.1038/s41589-018-0065-9
  46. Wing R, Drew H, Takano T, Broka C, Tanaka S, Itakura K, Dickerson RE (October 1980). "Crystal structure analysis of a complete turn of B-DNA". Nature. 287 (5784): 755–58. Bibcode:1980Natur.287..755W. doi:10.1038/287755a0. PMID   7432492.
  47. 1 2 Pabo CO, Sauer RT (1984). "Protein-DNA recognition". Annual Review of Biochemistry. 53: 293–321. doi:10.1146/annurev.bi.53.070184.001453. PMID   6236744.
  48. Nikolova EN, Zhou H, Gottardo FL, Alvey HS, Kimsey IJ, Al-Hashimi HM (2013). "A historical account of Hoogsteen base-pairs in duplex DNA". Biopolymers. 99 (12): 955–68. doi:10.1002/bip.22334. PMC   3844552 . PMID   23818176.
  49. Clausen-Schaumann H, Rief M, Tolksdorf C, Gaub HE (April 2000). "Mechanical stability of single DNA molecules". Biophysical Journal. 78 (4): 1997–2007. Bibcode:2000BpJ....78.1997C. doi:10.1016/S0006-3495(00)76747-6. PMC   1300792 . PMID   10733978.
  50. Chalikian TV, Völker J, Plum GE, Breslauer KJ (July 1999). "A more unified picture for the thermodynamics of nucleic acid duplex melting: a characterization by calorimetric and volumetric techniques". Proceedings of the National Academy of Sciences of the United States of America. 96 (14): 7853–58. Bibcode:1999PNAS...96.7853C. doi:10.1073/pnas.96.14.7853. PMC   22151 . PMID   10393911.
  51. deHaseth PL, Helmann JD (June 1995). "Open complex formation by Escherichia coli RNA polymerase: the mechanism of polymerase-induced strand separation of double helical DNA". Molecular Microbiology. 16 (5): 817–24. doi:10.1111/j.1365-2958.1995.tb02309.x. PMID   7476180.
  52. Isaksson J, Acharya S, Barman J, Cheruku P, Chattopadhyaya J (December 2004). "Single-stranded adenine-rich DNA and RNA retain structural characteristics of their respective double-stranded conformations and show directional differences in stacking pattern" (PDF). Biochemistry. 43 (51): 15996–6010. doi:10.1021/bi048221v. PMID   15609994. Archived (PDF) from the original on 10 June 2007.
  53. Designation of the two strands of DNA Archived 24 April 2008 at the Wayback Machine JCBN/NC-IUB Newsletter 1989. Retrieved 7 May 2008
  54. Hüttenhofer A, Schattner P, Polacek N (May 2005). "Non-coding RNAs: hope or hype?". Trends in Genetics. 21 (5): 289–97. doi:10.1016/j.tig.2005.03.007. PMID   15851066.
  55. Munroe SH (November 2004). "Diversity of antisense regulation in eukaryotes: multiple mechanisms, emerging patterns". Journal of Cellular Biochemistry. 93 (4): 664–71. doi:10.1002/jcb.20252. PMID   15389973.
  56. Makalowska I, Lin CF, Makalowski W (February 2005). "Overlapping genes in vertebrate genomes". Computational Biology and Chemistry. 29 (1): 1–12. doi:10.1016/j.compbiolchem.2004.12.006. PMID   15680581.
  57. Johnson ZI, Chisholm SW (November 2004). "Properties of overlapping genes are conserved across microbial genomes". Genome Research. 14 (11): 2268–72. doi:10.1101/gr.2433104. PMC   525685 . PMID   15520290.
  58. Lamb RA, Horvath CM (August 1991). "Diversity of coding strategies in influenza viruses". Trends in Genetics. 7 (8): 261–66. doi:10.1016/0168-9525(91)90326-L. PMID   1771674.
  59. Benham CJ, Mielke SP (2005). "DNA mechanics". Annual Review of Biomedical Engineering. 7: 21–53. doi:10.1146/annurev.bioeng.6.062403.132016. PMID   16004565.
  60. 1 2 Champoux JJ (2001). "DNA topoisomerases: structure, function, and mechanism". Annual Review of Biochemistry. 70: 369–413. doi:10.1146/annurev.biochem.70.1.369. PMID   11395412.
  61. 1 2 Wang JC (June 2002). "Cellular roles of DNA topoisomerases: a molecular perspective". Nature Reviews Molecular Cell Biology. 3 (6): 430–40. doi:10.1038/nrm831. PMID   12042765.
  62. Basu HS, Feuerstein BG, Zarling DA, Shafer RH, Marton LJ (October 1988). "Recognition of Z-RNA and Z-DNA determinants by polyamines in solution: experimental and theoretical studies". Journal of Biomolecular Structure & Dynamics. 6 (2): 299–309. doi:10.1080/07391102.1988.10507714. PMID   2482766.
  63. Franklin RE, Gosling RG (6 March 1953). "The Structure of Sodium Thymonucleate Fibres I. The Influence of Water Content" (PDF). Acta Crystallogr. 6 (8–9): 673–77. doi:10.1107/S0365110X53001939. Archived (PDF) from the original on 9 January 2016.
    Franklin RE, Gosling RG (1953). "The structure of sodium thymonucleate fibres. II. The cylindrically symmetrical Patterson function". Acta Crystallogr. 6 (8–9): 678–85. doi:10.1107/S0365110X53001940.
  64. 1 2 Franklin RE, Gosling RG (April 1953). "Molecular configuration in sodium thymonucleate" (PDF). Nature. 171 (4356): 740–41. Bibcode:1953Natur.171..740F. doi:10.1038/171740a0. PMID   13054694. Archived (PDF) from the original on 3 January 2011.
  65. 1 2 Wilkins MH, Stokes AR, Wilson HR (April 1953). "Molecular structure of deoxypentose nucleic acids" (PDF). Nature. 171 (4356): 738–40. Bibcode:1953Natur.171..738W. doi:10.1038/171738a0. PMID   13054693. Archived (PDF) from the original on 13 May 2011.
  66. Leslie AG, Arnott S, Chandrasekaran R, Ratliff RL (October 1980). "Polymorphism of DNA double helices". Journal of Molecular Biology. 143 (1): 49–72. doi:10.1016/0022-2836(80)90124-2. PMID   7441761.
  67. Baianu IC (1980). "Structural Order and Partial Disorder in Biological systems". Bull. Math. Biol. 42 (4): 137–41. doi:10.1007/BF02462372.
  68. Hosemann R, Bagchi RN (1962). Direct analysis of diffraction by matter. Amsterdam – New York: North-Holland Publishers.
  69. Baianu IC (1978). "X-ray scattering by partially disordered membrane systems". Acta Crystallogr A. 34 (5): 751–53. Bibcode:1978AcCrA..34..751B. doi:10.1107/S0567739478001540.
  70. Wahl MC, Sundaralingam M (1997). "Crystal structures of A-DNA duplexes". Biopolymers. 44 (1): 45–63. doi:10.1002/(SICI)1097-0282(1997)44:1<45::AID-BIP4>3.0.CO;2-#. PMID   9097733.
  71. Lu XJ, Shakked Z, Olson WK (July 2000). "A-form conformational motifs in ligand-bound DNA structures". Journal of Molecular Biology. 300 (4): 819–40. doi:10.1006/jmbi.2000.3690. PMID   10891271.
  72. Rothenburg S, Koch-Nolte F, Haag F (December 2001). "DNA methylation and Z-DNA formation as mediators of quantitative differences in the expression of alleles". Immunological Reviews. 184: 286–98. doi:10.1034/j.1600-065x.2001.1840125.x. PMID   12086319.
  73. Oh DB, Kim YG, Rich A (December 2002). "Z-DNA-binding proteins can act as potent effectors of gene expression in vivo". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16666–71. Bibcode:2002PNAS...9916666O. doi:10.1073/pnas.262672699. PMC   139201 . PMID   12486233.
  74. 1 2 Palmer J (2 December 2010). "Arsenic-loving bacteria may help in hunt for alien life". BBC News. Archived from the original on 3 December 2010. Retrieved 2 December 2010.
  75. 1 2 Bortman, Henry (2 December 2010). "Arsenic-Eating Bacteria Opens New Possibilities for Alien Life". Space.com. Archived from the original on 4 December 2010. Retrieved 2 December 2010.
  76. Katsnelson A (2 December 2010). "Arsenic-eating microbe may redefine chemistry of life". Nature News. doi:10.1038/news.2010.645. Archived from the original on 12 February 2012.
  77. Cressey D (3 October 2012). "'Arsenic-life' Bacterium Prefers Phosphorus after all". Nature News. doi:10.1038/nature.2012.11520.
  78. 1 2 Greider CW, Blackburn EH (December 1985). "Identification of a specific telomere terminal transferase activity in Tetrahymena extracts". Cell. 43 (2 Pt 1): 405–13. doi:10.1016/0092-8674(85)90170-9. PMID   3907856.
  79. 1 2 3 Nugent CI, Lundblad V (April 1998). "The telomerase reverse transcriptase: components and regulation". Genes & Development. 12 (8): 1073–85. doi:10.1101/gad.12.8.1073. PMID   9553037.
  80. Wright WE, Tesmer VM, Huffman KE, Levene SD, Shay JW (November 1997). "Normal human chromosomes have long G-rich telomeric overhangs at one end". Genes & Development. 11 (21): 2801–09. doi:10.1101/gad.11.21.2801. PMC   316649 . PMID   9353250.
  81. Created from Archived 17 October 2016 at the Wayback Machine
  82. 1 2 Burge S, Parkinson GN, Hazel P, Todd AK, Neidle S (2006). "Quadruplex DNA: sequence, topology and structure". Nucleic Acids Research. 34 (19): 5402–15. doi:10.1093/nar/gkl655. PMC   1636468 . PMID   17012276.
  83. Parkinson GN, Lee MP, Neidle S (June 2002). "Crystal structure of parallel quadruplexes from human telomeric DNA". Nature. 417 (6891): 876–80. Bibcode:2002Natur.417..876P. doi:10.1038/nature755. PMID   12050675.
  84. Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H, de Lange T (May 1999). "Mammalian telomeres end in a large duplex loop". Cell. 97 (4): 503–14. doi:10.1016/S0092-8674(00)80760-6. PMID   10338214.
  85. Seeman NC (November 2005). "DNA enables nanoscale control of the structure of matter". Quarterly Reviews of Biophysics. 38 (4): 363–71. doi:10.1017/S0033583505004087. PMC   3478329 . PMID   16515737.
  86. Warren M (21 February 2019). "Four new DNA letters double life's alphabet". Nature. 566: 436. doi:10.1038/d41586-019-00650-8.
  87. Hoshika S, Leal NA, Kim MJ, Kim MS, Karalkar NB, Kim HJ, et al. (22 February 2019). "Hachimoji DNA and RNA: A genetic system with eight building blocks (paywall)". Science . 363 (6429): 884–887. doi:10.1126/science.aat0971 . Retrieved 24 February 2019.
  88. Hu Q, Rosenfeld MG (2012). "Epigenetic regulation of human embryonic stem cells". Frontiers in Genetics. 3: 238. doi:10.3389/fgene.2012.00238. PMC   3488762 . PMID   23133442.
  89. Klose RJ, Bird AP (February 2006). "Genomic DNA methylation: the mark and its mediators". Trends in Biochemical Sciences. 31 (2): 89–97. doi:10.1016/j.tibs.2005.12.008. PMID   16403636.
  90. Bird A (January 2002). "DNA methylation patterns and epigenetic memory". Genes & Development. 16 (1): 6–21. doi:10.1101/gad.947102. PMID   11782440.
  91. Walsh CP, Xu GL (2006). "Cytosine methylation and DNA repair". Current Topics in Microbiology and Immunology. Current Topics in Microbiology and Immunology. 301: 283–315. doi:10.1007/3-540-31390-7_11. ISBN   3-540-29114-8. PMID   16570853.
  92. Kriaucionis S, Heintz N (May 2009). "The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain". Science. 324 (5929): 929–30. Bibcode:2009Sci...324..929K. doi:10.1126/science.1169786. PMC   3263819 . PMID   19372393.
  93. Ratel D, Ravanat JL, Berger F, Wion D (March 2006). "N6-methyladenine: the other methylated base of DNA". BioEssays. 28 (3): 309–15. doi:10.1002/bies.20342. PMC   2754416 . PMID   16479578.
  94. Gommers-Ampt JH, Van Leeuwen F, de Beer AL, Vliegenthart JF, Dizdaroglu M, Kowalak JA, Crain PF, Borst P (December 1993). "beta-D-glucosyl-hydroxymethyluracil: a novel modified base present in the DNA of the parasitic protozoan T. brucei". Cell. 75 (6): 1129–36. doi:10.1016/0092-8674(93)90322-H. PMID   8261512.
  95. Created from PDB 1JDG
  96. Douki T, Reynaud-Angelin A, Cadet J, Sage E (August 2003). "Bipyrimidine photoproducts rather than oxidative lesions are the main type of DNA damage involved in the genotoxic effect of solar UVA radiation". Biochemistry. 42 (30): 9221–26. doi:10.1021/bi034593c. PMID   12885257.
  97. Cadet J, Delatour T, Douki T, Gasparutto D, Pouget JP, Ravanat JL, Sauvaigo S (March 1999). "Hydroxyl radicals and DNA base damage". Mutation Research. 424 (1–2): 9–21. doi:10.1016/S0027-5107(99)00004-4. PMID   10064846.
  98. Beckman KB, Ames BN (August 1997). "Oxidative decay of DNA". The Journal of Biological Chemistry. 272 (32): 19633–36. doi:10.1074/jbc.272.32.19633. PMID   9289489.
  99. Valerie K, Povirk LF (September 2003). "Regulation and mechanisms of mammalian double-strand break repair". Oncogene. 22 (37): 5792–812. doi:10.1038/sj.onc.1206679. PMID   12947387.
  100. Johnson G (28 December 2010). "Unearthing Prehistoric Tumors, and Debate". The New York Times . Archived from the original on 24 June 2017. If we lived long enough, sooner or later we all would get cancer.
  101. Alberts B, Johnson A, Lewis J, et al. (2002). "The Preventable Causes of Cancer". Molecular biology of the cell (4th ed.). New York: Garland Science. ISBN   0-8153-4072-9. Archived from the original on 2 January 2016. A certain irreducible background incidence of cancer is to be expected regardless of circumstances: mutations can never be absolutely avoided, because they are an inescapable consequence of fundamental limitations on the accuracy of DNA replication, as discussed in Chapter 5. If a human could live long enough, it is inevitable that at least one of his or her cells would eventually accumulate a set of mutations sufficient for cancer to develop.
  102. Bernstein H, Payne CM, Bernstein C, Garewal H, Dvorak K (2008). "Cancer and aging as consequences of un-repaired DNA damage". In Kimura H, Suzuki A (eds.). New Research on DNA Damage. New York: Nova Science Publishers. pp. 1–47. ISBN   978-1-60456-581-2. Archived from the original on 25 October 2014.
  103. Hoeijmakers JH (October 2009). "DNA damage, aging, and cancer". The New England Journal of Medicine. 361 (15): 1475–85. doi:10.1056/NEJMra0804615. PMID   19812404.
  104. Freitas AA, de Magalhães JP (2011). "A review and appraisal of the DNA damage theory of ageing". Mutation Research. 728 (1–2): 12–22. doi:10.1016/j.mrrev.2011.05.001. PMID   21600302.
  105. Ferguson LR, Denny WA (September 1991). "The genetic toxicology of acridines". Mutation Research. 258 (2): 123–60. doi:10.1016/0165-1110(91)90006-H. PMID   1881402.
  106. Stephens TD, Bunde CJ, Fillmore BJ (June 2000). "Mechanism of action in thalidomide teratogenesis". Biochemical Pharmacology. 59 (12): 1489–99. doi:10.1016/S0006-2952(99)00388-3. PMID   10799645.
  107. Jeffrey AM (1985). "DNA modification by chemical carcinogens". Pharmacology & Therapeutics. 28 (2): 237–72. doi:10.1016/0163-7258(85)90013-0. PMID   3936066.
  108. Braña MF, Cacho M, Gradillas A, de Pascual-Teresa B, Ramos A (November 2001). "Intercalators as anticancer drugs". Current Pharmaceutical Design. 7 (17): 1745–80. doi:10.2174/1381612013397113. PMID   11562309.
  109. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, et al. (February 2001). "The sequence of the human genome". Science. 291 (5507): 1304–51. Bibcode:2001Sci...291.1304V. doi:10.1126/science.1058040. PMID   11181995.
  110. Thanbichler M, Wang SC, Shapiro L (October 2005). "The bacterial nucleoid: a highly organized and dynamic structure". Journal of Cellular Biochemistry. 96 (3): 506–21. doi:10.1002/jcb.20519. PMID   15988757.
  111. Wolfsberg TG, McEntyre J, Schuler GD (February 2001). "Guide to the draft human genome". Nature. 409 (6822): 824–26. Bibcode:2001Natur.409..824W. doi:10.1038/35057000. PMID   11236998.
  112. Gregory TR (January 2005). "The C-value enigma in plants and animals: a review of parallels and an appeal for partnership". Annals of Botany. 95 (1): 133–46. doi:10.1093/aob/mci009. PMC   4246714 . PMID   15596463.
  113. Birney E, Stamatoyannopoulos JA, Dutta A, Guigó R, Gingeras TR, Margulies EH, et al. (June 2007). "Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project". Nature. 447 (7146): 799–816. Bibcode:2007Natur.447..799B. doi:10.1038/nature05874. PMC   2212820 . PMID   17571346.
  114. Created from PDB 1MSW Archived 6 January 2008 at the Wayback Machine
  115. Pidoux AL, Allshire RC (March 2005). "The role of heterochromatin in centromere function". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 360 (1455): 569–79. doi:10.1098/rstb.2004.1611. PMC   1569473 . PMID   15905142.
  116. Harrison PM, Hegyi H, Balasubramanian S, Luscombe NM, Bertone P, Echols N, Johnson T, Gerstein M (February 2002). "Molecular fossils in the human genome: identification and analysis of the pseudogenes in chromosomes 21 and 22". Genome Research. 12 (2): 272–80. doi:10.1101/gr.207102. PMC   155275 . PMID   11827946.
  117. Harrison PM, Gerstein M (May 2002). "Studying genomes through the aeons: protein families, pseudogenes and proteome evolution". Journal of Molecular Biology. 318 (5): 1155–74. doi:10.1016/S0022-2836(02)00109-2. PMID   12083509.
  118. Albà M (2001). "Replicative DNA polymerases". Genome Biology. 2 (1): REVIEWS3002. doi:10.1186/gb-2001-2-1-reviews3002. PMC   150442 . PMID   11178285.
  119. Tani K, Nasu M (2010). "Roles of Extracellular DNA in Bacterial Ecosystems". In Kikuchi Y, Rykova EY (eds.). Extracellular Nucleic Acids. Springer. pp. 25–38. ISBN   978-3-642-12616-1.
  120. Vlassov VV, Laktionov PP, Rykova EY (July 2007). "Extracellular nucleic acids". BioEssays. 29 (7): 654–67. doi:10.1002/bies.20604. PMID   17563084.
  121. Finkel SE, Kolter R (November 2001). "DNA as a nutrient: novel role for bacterial competence gene homologs". Journal of Bacteriology. 183 (21): 6288–93. doi:10.1128/JB.183.21.6288-6293.2001. PMC   100116 . PMID   11591672.
  122. Mulcahy H, Charron-Mazenod L, Lewenza S (November 2008). "Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms". PLoS Pathogens. 4 (11): e1000213. doi:10.1371/journal.ppat.1000213. PMC   2581603 . PMID   19023416.
  123. Berne C, Kysela DT, Brun YV (August 2010). "A bacterial extracellular DNA inhibits settling of motile progeny cells within a biofilm". Molecular Microbiology. 77 (4): 815–29. doi:10.1111/j.1365-2958.2010.07267.x. PMC   2962764 . PMID   20598083.
  124. Whitchurch CB, Tolker-Nielsen T, Ragas PC, Mattick JS (February 2002). "Extracellular DNA required for bacterial biofilm formation". Science. 295 (5559): 1487. doi:10.1126/science.295.5559.1487. PMID   11859186.
  125. Hu W, Li L, Sharma S, Wang J, McHardy I, Lux R, Yang Z, He X, Gimzewski JK, Li Y, Shi W (2012). "DNA builds and strengthens the extracellular matrix in Myxococcus xanthus biofilms by interacting with exopolysaccharides". PLOS ONE. 7 (12): e51905. Bibcode:2012PLoSO...751905H. doi:10.1371/journal.pone.0051905. PMC   3530553 . PMID   23300576.
  126. Hui L, Bianchi DW (February 2013). "Recent advances in the prenatal interrogation of the human fetal genome". Trends in Genetics. 29 (2): 84–91. doi:10.1016/j.tig.2012.10.013. PMC   4378900 . PMID   23158400.
  127. Sandman K, Pereira SL, Reeve JN (December 1998). "Diversity of prokaryotic chromosomal proteins and the origin of the nucleosome". Cellular and Molecular Life Sciences. 54 (12): 1350–64. doi:10.1007/s000180050259. PMID   9893710.
  128. Dame RT (May 2005). "The role of nucleoid-associated proteins in the organization and compaction of bacterial chromatin". Molecular Microbiology. 56 (4): 858–70. doi:10.1111/j.1365-2958.2005.04598.x. PMID   15853876.
  129. Luger K, Mäder AW, Richmond RK, Sargent DF, Richmond TJ (September 1997). "Crystal structure of the nucleosome core particle at 2.8 A resolution". Nature. 389 (6648): 251–60. Bibcode:1997Natur.389..251L. doi:10.1038/38444. PMID   9305837.
  130. Jenuwein T, Allis CD (August 2001). "Translating the histone code" (PDF). Science. 293 (5532): 1074–80. doi:10.1126/science.1063127. PMID   11498575. Archived (PDF) from the original on 8 August 2017.
  131. Ito T (2003). "Nucleosome assembly and remodeling". Current Topics in Microbiology and Immunology. Current Topics in Microbiology and Immunology. 274: 1–22. doi:10.1007/978-3-642-55747-7_1. ISBN   978-3-540-44208-0. PMID   12596902.
  132. Thomas JO (August 2001). "HMG1 and 2: architectural DNA-binding proteins". Biochemical Society Transactions. 29 (Pt 4): 395–401. doi:10.1042/BST0290395. PMID   11497996.
  133. Grosschedl R, Giese K, Pagel J (March 1994). "HMG domain proteins: architectural elements in the assembly of nucleoprotein structures". Trends in Genetics. 10 (3): 94–100. doi:10.1016/0168-9525(94)90232-1. PMID   8178371.
  134. Iftode C, Daniely Y, Borowiec JA (1999). "Replication protein A (RPA): the eukaryotic SSB". Critical Reviews in Biochemistry and Molecular Biology. 34 (3): 141–80. doi:10.1080/10409239991209255. PMID   10473346.
  135. Created from PDB 1LMB Archived 6 January 2008 at the Wayback Machine
  136. Myers LC, Kornberg RD (2000). "Mediator of transcriptional regulation". Annual Review of Biochemistry. 69: 729–49. doi:10.1146/annurev.biochem.69.1.729. PMID   10966474.
  137. Spiegelman BM, Heinrich R (October 2004). "Biological control through regulated transcriptional coactivators". Cell. 119 (2): 157–67. doi:10.1016/j.cell.2004.09.037. PMID   15479634.
  138. Li Z, Van Calcar S, Qu C, Cavenee WK, Zhang MQ, Ren B (July 2003). "A global transcriptional regulatory role for c-Myc in Burkitt's lymphoma cells". Proceedings of the National Academy of Sciences of the United States of America. 100 (14): 8164–69. Bibcode:2003PNAS..100.8164L. doi:10.1073/pnas.1332764100. PMC   166200 . PMID   12808131.
  139. Created from PDB 1RVA Archived 6 January 2008 at the Wayback Machine
  140. Bickle TA, Krüger DH (June 1993). "Biology of DNA restriction". Microbiological Reviews. 57 (2): 434–50. PMC   372918 . PMID   8336674.
  141. 1 2 Doherty AJ, Suh SW (November 2000). "Structural and mechanistic conservation in DNA ligases". Nucleic Acids Research. 28 (21): 4051–58. doi:10.1093/nar/28.21.4051. PMC   113121 . PMID   11058099.
  142. Schoeffler AJ, Berger JM (December 2005). "Recent advances in understanding structure-function relationships in the type II topoisomerase mechanism". Biochemical Society Transactions. 33 (Pt 6): 1465–70. doi:10.1042/BST20051465. PMID   16246147.
  143. Tuteja N, Tuteja R (May 2004). "Unraveling DNA helicases. Motif, structure, mechanism and function". European Journal of Biochemistry. 271 (10): 1849–63. doi:10.1111/j.1432-1033.2004.04094.x. PMID   15128295.
  144. Joyce CM, Steitz TA (November 1995). "Polymerase structures and function: variations on a theme?". Journal of Bacteriology. 177 (22): 6321–29. doi:10.1128/jb.177.22.6321-6329.1995. PMC   177480 . PMID   7592405.
  145. Hubscher U, Maga G, Spadari S (2002). "Eukaryotic DNA polymerases". Annual Review of Biochemistry. 71: 133–63. doi:10.1146/annurev.biochem.71.090501.150041. PMID   12045093.
  146. Johnson A, O'Donnell M (2005). "Cellular DNA replicases: components and dynamics at the replication fork". Annual Review of Biochemistry. 74: 283–315. doi:10.1146/annurev.biochem.73.011303.073859. PMID   15952889.
  147. 1 2 Tarrago-Litvak L, Andréola ML, Nevinsky GA, Sarih-Cottin L, Litvak S (May 1994). "The reverse transcriptase of HIV-1: from enzymology to therapeutic intervention". FASEB Journal. 8 (8): 497–503. PMID   7514143.
  148. Martinez E (December 2002). "Multi-protein complexes in eukaryotic gene transcription". Plant Molecular Biology. 50 (6): 925–47. doi:10.1023/A:1021258713850. PMID   12516863.
  149. Created from PDB 1M6G Archived 10 January 2010 at the Wayback Machine
  150. Cremer T, Cremer C (April 2001). "Chromosome territories, nuclear architecture and gene regulation in mammalian cells". Nature Reviews Genetics. 2 (4): 292–301. doi:10.1038/35066075. PMID   11283701.
  151. Pál C, Papp B, Lercher MJ (May 2006). "An integrated view of protein evolution". Nature Reviews Genetics. 7 (5): 337–48. doi:10.1038/nrg1838. PMID   16619049.
  152. O'Driscoll M, Jeggo PA (January 2006). "The role of double-strand break repair – insights from human genetics". Nature Reviews Genetics. 7 (1): 45–54. doi:10.1038/nrg1746. PMID   16369571.
  153. Vispé S, Defais M (October 1997). "Mammalian Rad51 protein: a RecA homologue with pleiotropic functions". Biochimie. 79 (9–10): 587–92. doi:10.1016/S0300-9084(97)82007-X. PMID   9466696.
  154. Neale MJ, Keeney S (July 2006). "Clarifying the mechanics of DNA strand exchange in meiotic recombination". Nature. 442 (7099): 153–58. Bibcode:2006Natur.442..153N. doi:10.1038/nature04885. PMC   5607947 . PMID   16838012.
  155. Dickman MJ, Ingleston SM, Sedelnikova SE, Rafferty JB, Lloyd RG, Grasby JA, Hornby DP (November 2002). "The RuvABC resolvasome". European Journal of Biochemistry. 269 (22): 5492–501. doi:10.1046/j.1432-1033.2002.03250.x. PMID   12423347.
  156. Joyce GF (July 2002). "The antiquity of RNA-based evolution". Nature. 418 (6894): 214–21. Bibcode:2002Natur.418..214J. doi:10.1038/418214a. PMID   12110897.
  157. Orgel LE (2004). "Prebiotic chemistry and the origin of the RNA world". Critical Reviews in Biochemistry and Molecular Biology. 39 (2): 99–123. doi:10.1080/10409230490460765. PMID   15217990.
  158. Davenport RJ (May 2001). "Ribozymes. Making copies in the RNA world". Science. 292 (5520): 1278. doi:10.1126/science.292.5520.1278a. PMID   11360970.
  159. Szathmáry E (April 1992). "What is the optimum size for the genetic alphabet?". Proceedings of the National Academy of Sciences of the United States of America. 89 (7): 2614–18. Bibcode:1992PNAS...89.2614S. doi:10.1073/pnas.89.7.2614. PMC   48712 . PMID   1372984.
  160. Lindahl T (April 1993). "Instability and decay of the primary structure of DNA". Nature. 362 (6422): 709–15. Bibcode:1993Natur.362..709L. doi:10.1038/362709a0. PMID   8469282.
  161. Vreeland RH, Rosenzweig WD, Powers DW (October 2000). "Isolation of a 250 million-year-old halotolerant bacterium from a primary salt crystal". Nature. 407 (6806): 897–900. Bibcode:2000Natur.407..897V. doi:10.1038/35038060. PMID   11057666.
  162. Hebsgaard MB, Phillips MJ, Willerslev E (May 2005). "Geologically ancient DNA: fact or artefact?". Trends in Microbiology. 13 (5): 212–20. doi:10.1016/j.tim.2005.03.010. PMID   15866038.
  163. Nickle DC, Learn GH, Rain MW, Mullins JI, Mittler JE (January 2002). "Curiously modern DNA for a "250 million-year-old" bacterium". Journal of Molecular Evolution. 54 (1): 134–37. Bibcode:2002JMolE..54..134N. doi:10.1007/s00239-001-0025-x. PMID   11734907.
  164. Callahan MP, Smith KE, Cleaves HJ, Ruzicka J, Stern JC, Glavin DP, House CH, Dworkin JP (August 2011). "Carbonaceous meteorites contain a wide range of extraterrestrial nucleobases". Proceedings of the National Academy of Sciences of the United States of America. 108 (34): 13995–98. Bibcode:2011PNAS..10813995C. doi:10.1073/pnas.1106493108. PMC   3161613 . PMID   21836052.
  165. Steigerwald J (8 August 2011). "NASA Researchers: DNA Building Blocks Can Be Made in Space". NASA. Archived from the original on 23 June 2015. Retrieved 10 August 2011.
  166. ScienceDaily Staff (9 August 2011). "DNA Building Blocks Can Be Made in Space, NASA Evidence Suggests". ScienceDaily . Archived from the original on 5 September 2011. Retrieved 9 August 2011.
  167. Marlaire R (3 March 2015). "NASA Ames Reproduces the Building Blocks of Life in Laboratory". NASA . Archived from the original on 5 March 2015. Retrieved 5 March 2015.
  168. Goff SP, Berg P (December 1976). "Construction of hybrid viruses containing SV40 and lambda phage DNA segments and their propagation in cultured monkey cells". Cell. 9 (4 PT 2): 695–705. doi:10.1016/0092-8674(76)90133-1. PMID   189942.
  169. Houdebine LM (2007). "Transgenic animal models in biomedical research". Methods in Molecular Biology. 360: 163–202. doi:10.1385/1-59745-165-7:163. ISBN   1-59745-165-7. PMID   17172731.
  170. Daniell H, Dhingra A (April 2002). "Multigene engineering: dawn of an exciting new era in biotechnology". Current Opinion in Biotechnology. 13 (2): 136–41. doi:10.1016/S0958-1669(02)00297-5. PMC   3481857 . PMID   11950565.
  171. Job D (November 2002). "Plant biotechnology in agriculture". Biochimie. 84 (11): 1105–10. doi:10.1016/S0300-9084(02)00013-5. PMID   12595138.
  172. Curtis C, Hereward J (29 August 2017). "From the crime scene to the courtroom: the journey of a DNA sample". The Conversation. Archived from the original on 22 October 2017. Retrieved 22 October 2017.
  173. Collins A, Morton NE (June 1994). "Likelihood ratios for DNA identification". Proceedings of the National Academy of Sciences of the United States of America. 91 (13): 6007–11. Bibcode:1994PNAS...91.6007C. doi:10.1073/pnas.91.13.6007. PMC   44126 . PMID   8016106.
  174. Weir BS, Triggs CM, Starling L, Stowell LI, Walsh KA, Buckleton J (March 1997). "Interpreting DNA mixtures". Journal of Forensic Sciences. 42 (2): 213–22. PMID   9068179.
  175. Jeffreys AJ, Wilson V, Thein SL (1985). "Individual-specific 'fingerprints' of human DNA". Nature. 316 (6023): 76–79. Bibcode:1985Natur.316...76J. doi:10.1038/316076a0. PMID   2989708.
  176. Colin Pitchfork – first murder conviction on DNA evidence also clears the prime suspect Forensic Science Service Accessed 23 December 2006
  177. "DNA Identification in Mass Fatality Incidents". National Institute of Justice. September 2006. Archived from the original on 12 November 2006.
  178. "Paternity Blood Tests That Work Early in a Pregnancy" New York Times June 20, 2012 Archived 24 June 2017 at the Wayback Machine
  179. 1 2 Breaker RR, Joyce GF (December 1994). "A DNA enzyme that cleaves RNA". Chemistry & Biology. 1 (4): 223–29. doi:10.1016/1074-5521(94)90014-0. PMID   9383394.
  180. Chandra M, Sachdeva A, Silverman SK (October 2009). "DNA-catalyzed sequence-specific hydrolysis of DNA". Nature Chemical Biology. 5 (10): 718–20. doi:10.1038/nchembio.201. PMC   2746877 . PMID   19684594.
  181. Carmi N, Shultz LA, Breaker RR (December 1996). "In vitro selection of self-cleaving DNAs". Chemistry & Biology. 3 (12): 1039–46. doi:10.1016/S1074-5521(96)90170-2. PMID   9000012.
  182. Torabi SF, Wu P, McGhee CE, Chen L, Hwang K, Zheng N, Cheng J, Lu Y (May 2015). "In vitro selection of a sodium-specific DNAzyme and its application in intracellular sensing". Proceedings of the National Academy of Sciences of the United States of America. 112 (19): 5903–08. Bibcode:2015PNAS..112.5903T. doi:10.1073/pnas.1420361112. PMC   4434688 . PMID   25918425.
  183. Baldi P, Brunak S (2001). Bioinformatics: The Machine Learning Approach. MIT Press. ISBN   978-0-262-02506-5. OCLC   45951728.
  184. Gusfield, Dan (15 January 1997). Algorithms on Strings, Trees, and Sequences: Computer Science and Computational Biology. Cambridge University Press. ISBN   978-0-521-58519-4.
  185. Sjölander K (January 2004). "Phylogenomic inference of protein molecular function: advances and challenges". Bioinformatics. 20 (2): 170–79. doi:10.1093/bioinformatics/bth021. PMID   14734307.
  186. Mount DM (2004). Bioinformatics: Sequence and Genome Analysis (2nd ed.). Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press. ISBN   0-87969-712-1. OCLC   55106399.
  187. Rothemund PW (March 2006). "Folding DNA to create nanoscale shapes and patterns". Nature. 440 (7082): 297–302. Bibcode:2006Natur.440..297R. doi:10.1038/nature04586. PMID   16541064.
  188. Andersen ES, Dong M, Nielsen MM, Jahn K, Subramani R, Mamdouh W, Golas MM, Sander B, Stark H, Oliveira CL, Pedersen JS, Birkedal V, Besenbacher F, Gothelf KV, Kjems J (May 2009). "Self-assembly of a nanoscale DNA box with a controllable lid". Nature. 459 (7243): 73–76. Bibcode:2009Natur.459...73A. doi:10.1038/nature07971. PMID   19424153.
  189. Ishitsuka Y, Ha T (May 2009). "DNA nanotechnology: a nanomachine goes live". Nature Nanotechnology. 4 (5): 281–82. Bibcode:2009NatNa...4..281I. doi:10.1038/nnano.2009.101. PMID   19421208.
  190. Aldaye FA, Palmer AL, Sleiman HF (September 2008). "Assembling materials with DNA as the guide". Science. 321 (5897): 1795–99. Bibcode:2008Sci...321.1795A. doi:10.1126/science.1154533. PMID   18818351.
  191. Wray GA (2002). "Dating branches on the tree of life using DNA". Genome Biology. 3 (1): REVIEWS0001. doi:10.1186/gb-2001-3-1-reviews0001. PMC   150454 . PMID   11806830.
  192. Panda D, Molla KA, Baig MJ, Swain A, Behera D, Dash M (May 2018). "DNA as a digital information storage device: hope or hype?". 3 Biotech. 8 (5): 239. doi:10.1007/s13205-018-1246-7. PMC   5935598 . PMID   29744271.
  193. Akram F, Haq IU, Ali H, Laghari AT (October 2018). "Trends to store digital data in DNA: an overview". Molecular Biology Reports. 45 (5): 1479–1490. doi:10.1007/s11033-018-4280-y. PMID   30073589.
  194. Miescher F (1871). "Ueber die chemische Zusammensetzung der Eiterzellen" [On the chemical composition of pus cells]. Medicinisch-chemische Untersuchungen (in German). 4: 441–60. Ich habe mich daher später mit meinen Versuchen an die ganzen Kerne gehalten, die Trennung der Körper, die ich einstweilen ohne weiteres Präjudiz als lösliches und unlösliches Nuclein bezeichnen will, einem günstigeren Material überlassend. (Therefore, in my experiments I subsequently limited myself to the whole nucleus, leaving to a more favorable material the separation of the substances, that for the present, without further prejudice, I will designate as soluble and insoluble nuclear material ("Nuclein")
  195. Dahm R (January 2008). "Discovering DNA: Friedrich Miescher and the early years of nucleic acid research". Human Genetics. 122 (6): 565–81. doi:10.1007/s00439-007-0433-0. PMID   17901982.
  196. See:
    • Kossel A (1879). "Ueber Nucleïn der Hefe" [On nuclein in yeast]. Zeitschrift für physiologische Chemie (in German). 3: 284–91.
    • Kossel A (1880). "Ueber Nucleïn der Hefe II" [On nuclein in yeast, Part 2]. Zeitschrift für physiologische Chemie (in German). 4: 290–95.
    • Kossel A (1881). "Ueber die Verbreitung des Hypoxanthins im Thier- und Pflanzenreich" [On the distribution of hypoxanthins in the animal and plant kingdoms]. Zeitschrift für physiologische Chemie (in German). 5: 267–71.
    • Kossel A (1881). Trübne KJ (ed.). Untersuchungen über die Nucleine und ihre Spaltungsprodukte[Investigations into nuclein and its cleavage products] (in German). Strassburg, Germany. p. 19.
    • Kossel A (1882). "Ueber Xanthin und Hypoxanthin" [On xanthin and hypoxanthin]. Zeitschrift für physiologische Chemie. 6: 422–31.
    • Albrect Kossel (1883) "Zur Chemie des Zellkerns" Archived 17 November 2017 at the Wayback Machine (On the chemistry of the cell nucleus), Zeitschrift für physiologische Chemie, 7 : 7–22.
    • Kossel A (1886). "Weitere Beiträge zur Chemie des Zellkerns" [Further contributions to the chemistry of the cell nucleus]. Zeitschrift für Physiologische Chemie (in German). 10: 248–64. On p. 264, Kossel remarked presciently: Der Erforschung der quantitativen Verhältnisse der vier stickstoffreichen Basen, der Abhängigkeit ihrer Menge von den physiologischen Zuständen der Zelle, verspricht wichtige Aufschlüsse über die elementaren physiologisch-chemischen Vorgänge. (The study of the quantitative relations of the four nitrogenous bases—[and] of the dependence of their quantity on the physiological states of the cell—promises important insights into the fundamental physiological-chemical processes.)
  197. Jones ME (September 1953). "Albrecht Kossel, a biographical sketch". The Yale Journal of Biology and Medicine. National Center for Biotechnology Information. 26 (1): 80–97. PMC   2599350 . PMID   13103145.
  198. Levene PA, Jacobs WA (1909). "Über Inosinsäure". Berichte der deutschen chemischen Gesellschaft (in German). 42: 1198–203. doi:10.1002/cber.190904201196.
  199. Levene PA, Jacobs WA (1909). "Über die Hefe-Nucleinsäure". Berichte der deutschen chemischen Gesellschaft (in German). 42 (2): 2474–78. doi:10.1002/cber.190904202148.
  200. Levene P (1919). "The structure of yeast nucleic acid". J Biol Chem. 40 (2): 415–24.
  201. Cohen JS, Portugal FH (1974). "The search for the chemical structure of DNA" (PDF). Connecticut Medicine. 38 (10): 551–52, 554–57.
  202. Koltsov proposed that a cell's genetic information was encoded in a long chain of amino acids. See:
    • Кольцов, Н. К. (12 December 1927). Физико-химические основы морфологии[The physical-chemical basis of morphology] (Speech). 3rd All-Union Meeting of Zoologist, Anatomists, and Histologists (in Russian). Leningrad, U.S.S.R.
    • Reprinted in: Кольцов, Н. К. (1928). "Физико-химические основы морфологии" [The physical-chemical basis of morphology]. Успехи экспериментальной биологии (Advances in Experimental Biology) series B (in Russian). 7 (1): ?–?.
    • Reprinted in German as: Koltzoff NK (1928). "Physikalisch-chemische Grundlagen der Morphologie" [The physical-chemical basis of morphology]. Biologisches Zentralblatt (in German). 48 (6): 345–69.
    • In 1934, Koltsov contended that the proteins that contain a cell's genetic information replicate. See: Koltzoff N (October 1934). "The structure of the chromosomes in the salivary glands of Drosophila". Science. 80 (2075): 312–13. Bibcode:1934Sci....80..312K. doi:10.1126/science.80.2075.312. PMID   17769043. From page 313: "I think that the size of the chromosomes in the salivary glands [of Drosophila] is determined through the multiplication of genonemes. By this term I designate the axial thread of the chromosome, in which the geneticists locate the linear combination of genes; … In the normal chromosome there is usually only one genoneme; before cell-division this genoneme has become divided into two strands."
  203. Soyfer VN (September 2001). "The consequences of political dictatorship for Russian science". Nature Reviews Genetics. 2 (9): 723–29. doi:10.1038/35088598. PMID   11533721.
  204. Griffith F (January 1928). "The Significance of Pneumococcal Types". The Journal of Hygiene. 27 (2): 113–59. doi:10.1017/S0022172400031879. PMC   2167760 . PMID   20474956.
  205. Lorenz MG, Wackernagel W (September 1994). "Bacterial gene transfer by natural genetic transformation in the environment". Microbiological Reviews. 58 (3): 563–602. PMC   372978 . PMID   7968924.
  206. Brachet J (1933). "Recherches sur la synthese de l'acide thymonucleique pendant le developpement de l'oeuf d'Oursin". Archives de Biologie (in Italian). 44: 519–76.
  207. Burian R (1994). "Jean Brachet's Cytochemical Embryology: Connections with the Renovation of Biology in France?". In Debru C, Gayon J, Picard JF (eds.). Les sciences biologiques et médicales en France 1920–1950 (PDF). Cahiers pour I'histoire de la recherche. 2. Paris: CNRS Editions. pp. 207–20.
  208. See:
  209. Avery OT, Macleod CM, McCarty M (February 1944). "Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III". The Journal of Experimental Medicine. 79 (2): 137–58. doi:10.1084/jem.79.2.137. PMC   2135445 . PMID   19871359.
  210. Hershey AD, Chase M (May 1952). "Independent functions of viral protein and nucleic acid in growth of bacteriophage". The Journal of General Physiology. 36 (1): 39–56. doi:10.1085/jgp.36.1.39. PMC   2147348 . PMID   12981234.
  211. The B-DNA X-ray pattern on the right of this linked image Archived 25 May 2012 at Archive.today was obtained by Rosalind Franklin and Raymond Gosling in May 1952 at high hydration levels of DNA and it has been labeled as "Photo 51"
  212. Regis E (2009). What Is Life?: investigating the nature of life in the age of synthetic biology. Oxford: Oxford University Press. p. 52. ISBN   0-19-538341-9.
  213. Pauling L, Corey RB (February 1953). "A Proposed Structure For The Nucleic Acids". Proceedings of the National Academy of Sciences of the United States of America. 39 (2): 84–97. doi:10.1073/pnas.39.2.84. PMC   1063734 . PMID   16578429.
  214. "Double Helix of DNA: 50 Years". Nature Archives. Archived from the original on 5 April 2015.
  215. "Original X-ray diffraction image". Oregon State Library. Archived from the original on 30 January 2009. Retrieved 6 February 2011.
  216. "The Nobel Prize in Physiology or Medicine 1962". Nobelprize.org.
  217. Maddox B (January 2003). "The double helix and the 'wronged heroine'" (PDF). Nature. 421 (6921): 407–08. Bibcode:2003Natur.421..407M. doi:10.1038/nature01399. PMID   12540909. Archived (PDF) from the original on 17 October 2016.
  218. Crick F (1955). A Note for the RNA Tie Club (PDF) (Speech). Cambridge, England. Archived from the original (PDF) on 1 October 2008.
  219. Meselson M, Stahl FW (July 1958). "The Replication of DNA in Escherichia Coli". Proceedings of the National Academy of Sciences of the United States of America. 44 (7): 671–82. Bibcode:1958PNAS...44..671M. doi:10.1073/pnas.44.7.671. PMC   528642 . PMID   16590258.
  220. "The Nobel Prize in Physiology or Medicine 1968". Nobelprize.org.
  221. Pray L (2008). "Discovery of DNA structure and function: Watson and Crick". Nature Education. 1 (1): 100.

Further reading