DNA supercoil

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Supercoiled structure of circular DNA molecules with low writhe. The helical nature of the DNA duplex is omitted for clarity. Circular DNA Supercoiling.png
Supercoiled structure of circular DNA molecules with low writhe. The helical nature of the DNA duplex is omitted for clarity.
Supercoiled structure of linear DNA molecules with constrained ends. The helical nature of the DNA duplex is omitted for clarity. Linear DNA Supercoiling.png
Supercoiled structure of linear DNA molecules with constrained ends. The helical nature of the DNA duplex is omitted for clarity.

DNA supercoiling refers to the amount of twist in a particular DNA strand, which determines the amount of strain on it. A given strand may be "positively supercoiled" or "negatively supercoiled" (more or less tightly wound). The amount of a strand's supercoiling affects a number of biological processes, such as compacting DNA and regulating access to the genetic code (which strongly affects DNA metabolism and possibly gene expression). Certain enzymes, such as topoisomerases, change the amount of DNA supercoiling to facilitate functions such as DNA replication and transcription. [1] The amount of supercoiling in a given strand is described by a mathematical formula that compares it to a reference state known as "relaxed B-form" DNA.

Contents

Overview

In a "relaxed" double-helical segment of B-DNA, the two strands twist around the helical axis once every 10.4–10.5 base pairs of sequence. Adding or subtracting twists, as some enzymes do, imposes strain. If a DNA segment under twist strain is closed into a circle by joining its two ends, and then allowed to move freely, it takes on different shape, such as a figure-eight. This shape is referred to as a supercoil. (The noun form "supercoil" is often used when describing DNA topology.)

The DNA of most organisms is usually negatively supercoiled. It becomes temporarily positively supercoiled when it is being replicated or transcribed. These processes are inhibited (regulated) if it is not promptly relaxed. The simplest shape of a supercoil is a figure eight; a circular DNA strand assumes this shape to accommodate more or few helical twists. The two lobes of the figure eight will appear rotated either clockwise or counterclockwise with respect to one another, depending on whether the helix is over- or underwound. For each additional helical twist being accommodated, the lobes will show one more rotation about their axis. [2]

Lobal contortions of a circular DNA, such as the rotation of the figure-eight lobes above, are referred to as writhe . The above example illustrates that twist and writhe are interconvertible. Supercoiling can be represented mathematically by the sum of twist and writhe. The twist is the number of helical turns in the DNA and the writhe is the number of times the double helix crosses over on itself (these are the supercoils). Extra helical twists are positive and lead to positive supercoiling, while subtractive twisting causes negative supercoiling. Many topoisomerase enzymes sense supercoiling and either generate or dissipate it as they change DNA topology.

In part because chromosomes may be very large, segments in the middle may act as if their ends are anchored. As a result, they may be unable to distribute excess twist to the rest of the chromosome or to absorb twist to recover from underwinding—the segments may become supercoiled, in other words. In response to supercoiling, they will assume an amount of writhe, just as if their ends were joined.

Supercoiled DNA forms two structures; a plectoneme or a toroid, or a combination of both. A negatively supercoiled DNA molecule will produce either a one-start left-handed helix, the toroid, or a two-start right-handed helix with terminal loops, the plectoneme. Plectonemes are typically more common in nature, and this is the shape most bacterial plasmids will take. For larger molecules it is common for hybrid structures to form – a loop on a toroid can extend into a plectoneme. If all the loops on a toroid extend then it becomes a branch point in the plectonemic structure. DNA supercoiling is important for DNA packaging within all cells, and seems to also play a role in gene expression. [3] [4]

Intercalation-induced supercoiling of DNA

Based on the properties of intercalating molecules, i.e. fluorescing upon binding to DNA and unwinding of DNA base-pairs, in 2016, a single-molecule technique has been introduced to directly visualize individual plectonemes along supercoiled DNA [5] which would further allow to study the interactions of DNA processing proteins with supercoiled DNA. In that study, Sytox Orange (an intercalating dye) was used to induce supercoiling on surface tethered DNA molecules.

Using this assay, it was found that the DNA sequence encodes for the position of plectonemic supercoils. [6] Furthermore, DNA supercoils were found to be enriched at the transcription start sites in prokaryotes.

Functions

Genome packaging

DNA supercoiling is important for DNA packaging within all cells. Because the length of DNA can be thousands of times that of a cell, packaging this genetic material into the cell or nucleus (in eukaryotes) is a difficult feat. Supercoiling of DNA reduces the space and allows for DNA to be packaged. In prokaryotes, plectonemic supercoils are predominant, because of the circular chromosome and relatively small amount of genetic material. In eukaryotes, DNA supercoiling exists on many levels of both plectonemic and solenoidal supercoils, with the solenoidal supercoiling proving most effective in compacting the DNA. Solenoidal supercoiling is achieved with histones to form a 10 nm fiber. This fiber is further coiled into a 30 nm fiber, and further coiled upon itself numerous times more.

DNA packaging is greatly increased during mitosis when duplicated sister DNAs are segregated into daughter cells. It has been shown that condensin, a large protein complex that plays a central role in mitotic chromosome assembly, induces positive supercoils in an ATP hydrolysis-dependent manner in vitro. [7] [8] Supercoiling could also play an important role during interphase in the formation and maintenance of topologically associating domains (TADs). [9]

Supercoiling is also required for DNA/RNA synthesis. Because DNA must be unwound for DNA/RNA polymerase action, supercoils will result. The region ahead of the polymerase complex will be unwound; this stress is compensated with positive supercoils ahead of the complex. Behind the complex, DNA is rewound and there will be compensatory negative supercoils. Topoisomerases such as DNA gyrase (Type II Topoisomerase) play a role in relieving some of the stress during DNA/RNA synthesis. [10]

In many bacterial species, barriers to supercoil diffusion divide the genome into a series of topologically isolated supercoil domains (SDs). [11] These SDs play a major role in organizing the nucleoid. SDs negatively supercoiled on average but can sometimes be positively supercoiled as well. The degree of supercoiling can vary in response to different forms of stress and influences the binding of different nucleoid associated proteins (NAPs) that further organize the bacterial genome. [12] For example, Dps from E. coli has been shown to bind supercoiled DNA much more rapidly that torsionally relaxed DNA. [13]

Gene expression

Specialized proteins can unzip small segments of the DNA molecule when it is replicated or transcribed into RNA. But work published in 2015 illustrates how DNA opens on its own. [3] [4]

Simply twisting DNA can expose internal bases to the outside, without the aid of any proteins. Also, transcription itself contorts DNA in living human cells, tightening some parts of the coil and loosening it in others. That stress triggers changes in shape, most notably opening up the helix to be read. Unfortunately, these interactions are very difficult to study because biological molecules morph shapes so easily. In 2008 it was noted that transcription twists DNA, leaving a trail of undercoiled (or negatively supercoiled) DNA in its wake. Moreover, they discovered that the DNA sequence itself affects how the molecule responds to supercoiling. [3] [4]

For example, the researchers identified a specific sequence of DNA that regulates transcription speed; as the amount of supercoil rises and falls, it slows or speeds the pace at which molecular machinery reads DNA. [3] It is hypothesized that these structural changes might trigger stress elsewhere along its length, which in turn might provide trigger points for replication or gene expression. [3] [4] This implies that it is a very dynamic process in which both DNA and proteins each influences how the other acts and reacts. [3]

Gene Expression during cold shock

Almost half of the genes of the bacterium E. coli that are repressed during cold shock are similarly repressed when Gyrase is blocked by the antibiotic Novobiocin. [14] Moreover, during cold shocks, the density of nucleoids increases, and the protein gyrase and the nucleoid become colocalized (which is consistent with a reduction in DNA relaxation). This is evidence that the reduction of negative supercoiling of the DNA is one of the main mechanisms responsible for the blocking of transcription of half of the genes that conduct the cold shock transcriptional response program of bacteria. Based on this, a stochastic model of this process has been proposed. This model is illustrated in the figure, where reactions 1 represent transcription and its locking due to supercoiling. Meanwhile, reactions 2 to 4 model, respectively, translation, and RNA and protein degradation. [14]

Illustration of how cold shock affects the supercoiling state of the DNA, by blocking the activity of Gyrase. The signs ' - ' and '+' represent negative and positive supercoiling, respectively. Created with BioRender.com. Also shown is a stochastic model of gene expression during cold shock as a function of the global DNA supercoiling state. The transition from ON to OFF of the promoter (P) causes the locking of transcription (i.e. RNA production). When ON, the promoter can produce RNA, from which proteins can be produced. RNA and proteins are always subject to degradation or dilution due to cell division. Wikipedia ColdShock 2022CPASR.png
Illustration of how cold shock affects the supercoiling state of the DNA, by blocking the activity of Gyrase. The signs ' − ' and '+' represent negative and positive supercoiling, respectively. Created with BioRender.com. Also shown is a stochastic model of gene expression during cold shock as a function of the global DNA supercoiling state. The transition from ON to OFF of the promoter (P) causes the locking of transcription (i.e. RNA production). When ON, the promoter can produce RNA, from which proteins can be produced. RNA and proteins are always subject to degradation or dilution due to cell division.

Mathematical description

Drawing showing the difference between a circular DNA chromosome (a plasmid) with a secondary helical twist only, and one containing an additional tertiary superhelical twist superimposed on the secondary helical winding. Helix vs superhelix.png
Drawing showing the difference between a circular DNA chromosome (a plasmid) with a secondary helical twist only, and one containing an additional tertiary superhelical twist superimposed on the secondary helical winding.

In nature, circular DNA is always isolated as a higher-order helix-upon-a-helix, known as a superhelix. In discussions of this subject, the Watson–Crick twist is referred to as a "secondary" winding, and the superhelices as a "tertiary" winding. The sketch at right indicates a "relaxed", or "open circular" Watson–Crick double-helix, and, next to it, a right-handed superhelix. The "relaxed" structure on the left is not found unless the chromosome is nicked; the superhelix is the form usually found in nature.

For purposes of mathematical computations, a right-handed superhelix is defined as having a "negative" number of superhelical turns, and a left-handed superhelix is defined as having a "positive" number of superhelical turns. In the drawing (shown at the right), both the secondary (i.e., "Watson–Crick") winding and the tertiary (i.e., "superhelical") winding are right-handed, hence the supertwists are negative (–3 in this example).

The superhelicity is presumed to be a result of underwinding, meaning that there is a deficiency in the number of secondary Watson–Crick twists. Such a chromosome will be strained, just as a macroscopic metal spring is strained when it is either overwound or unwound. In DNA which is thusly strained, supertwists will appear.

DNA supercoiling can be described numerically by changes in the linking number Lk. The linking number is the most descriptive property of supercoiled DNA. Lko, the number of turns in the relaxed (B type) DNA plasmid/molecule, is determined by dividing the total base pairs of the molecule by the relaxed bp/turn which, depending on reference is 10.4; [15] 10.5; [16] [17] 10.6. [18]

Lk is the number of crosses a single strand makes across the other, often visualized as the number of Watson–Crick twists found in a circular chromosome in a (usually imaginary) planar projection. This number is physically "locked in" at the moment of covalent closure of the chromosome, and cannot be altered without strand breakage.

The topology of the DNA is described by the equation below in which the linking number is equivalent to the sum of Tw, which is the number of twists or turns of the double helix, and Wr, which is the number of coils or "writhes." If there is a closed DNA molecule, the sum of Tw and Wr, or the linking number, does not change. However, there may be complementary changes in Tw and Wr without changing their sum:

Tw, called "twist," is the number of Watson–Crick twists in the chromosome when it is not constrained to lie in a plane. We have already seen that native DNA is usually found to be superhelical. If one goes around the superhelically twisted chromosome, counting secondary Watson–Crick twists, that number will be different from the number counted when the chromosome is constrained to lie flat. In general, the number of secondary twists in the native, supertwisted chromosome is expected to be the "normal" Watson–Crick winding number, meaning a single 10-base-pair helical twist for every 34 Å of DNA length.

Wr, called "writhe," is the number of superhelical twists. Since biological circular DNA is usually underwound, Lk will generally be less than Tw, which means that Wr will typically be negative.

If DNA is underwound, it will be under strain, exactly as a metal spring is strained when forcefully unwound, and that the appearance of supertwists will allow the chromosome to relieve its strain by taking on negative supertwists, which correct the secondary underwinding in accordance with the topology equation above.

The topology equation shows that there is a one-to-one relationship between changes in Tw and Wr. For example, if a secondary "Watson–Crick" twist is removed, then a right-handed supertwist must have been removed simultaneously (or, if the chromosome is relaxed, with no supertwists, then a left-handed supertwist must be added).

The change in the linking number, ΔLk, is the actual number of turns in the plasmid/molecule, Lk, minus the number of turns in the relaxed plasmid/molecule Lko:

If the DNA is negatively supercoiled, . The negative supercoiling implies that the DNA is underwound.

A standard expression independent of the molecule size is the "specific linking difference" or "superhelical density" denoted σ, which represents the number of turns added or removed relative to the total number of turns in the relaxed molecule/plasmid, indicating the level of supercoiling.

The Gibbs free energy associated with the coiling is given by the equation below [19]

The difference in Gibbs free energy between the supercoiled circular DNA and uncoiled circular DNA with N > 2000 bp is approximated by:

or, 16 cal/bp.

Since the linking number L of supercoiled DNA is the number of times the two strands are intertwined (and both strands remain covalently intact), L cannot change. The reference state (or parameter) L0 of a circular DNA duplex is its relaxed state. In this state, its writhe W = 0. Since L = T + W, in a relaxed state T = L. Thus, if we have a 400 bp relaxed circular DNA duplex, L ~ 40 (assuming ~10 bp per turn in B-DNA). Then T ~ 40.

Negative supercoils favor local unwinding of the DNA, allowing processes such as transcription, DNA replication, and recombination. Negative supercoiling is also thought to favour the transition between B-DNA and Z-DNA, and moderate the interactions of DNA binding proteins involved in gene regulation. [20]

Stochastic models

Some stochastic models have been proposed to account for the effects of positive supercoiling buildup (PSB) in gene expression dynamics (e.g. in bacterial gene expression), differing in, e.g., the level of detail. In general, the detail increases when adding processes affected by and affecting supercoiling. As this addition occurs, the complexity of the model increases.

For example, in [21] two models of different complexity are proposed. In the most detailed one, events were modeled at the nucleotide level, while in the other the events were modeled at the promoter region alone, and thus required much less events to be accounted for.

Stochastic, prokaryotic model of the dynamics of RNA production and transcription locking at the promoter region, due to PSB. FIG-Supercoil-model.tif
Stochastic, prokaryotic model of the dynamics of RNA production and transcription locking at the promoter region, due to PSB.

Examples of stochastic models that focus on the effects of PSB on a promoter's activity can be found in:. [22] [23] In general, such models include a promoter, Pro, which is the region of DNA controlling transcription and, thus, whose activity/locking is affected by PSB. Also included are RNA molecules (the product of transcription), RNA polymerases (RNAP) which control transcription, and Gyrases (G) which regulate PSB. Finally, there needs to be a means to quantify PSB on the DNA (i.e. the promoter) at any given moment. This can be done by having some component in the system that is produced over time (e.g., during transcription events) to represent positive supercoils, and that is removed by the action of Gyrases. The amount of this component can then be set to affect the rate of transcription.

Effects on sedimentation coefficient

Figure showing the various conformational changes which are observed in circular DNA at different pH. At a pH of about 12 (alkaline), there is a dip in the sedimentation coefficient, followed by a relentless increase up to a pH of about 13, at which pH the structure converts into the mysterious "Form IV". Circular DNA s vs pH.jpg
Figure showing the various conformational changes which are observed in circular DNA at different pH. At a pH of about 12 (alkaline), there is a dip in the sedimentation coefficient, followed by a relentless increase up to a pH of about 13, at which pH the structure converts into the mysterious "Form IV".

The topological properties of circular DNA are complex. In standard texts, these properties are invariably explained in terms of a helical model for DNA, but in 2008 it was noted that each topoisomer, negative or positive, adopts a unique and surprisingly wide distribution of three-dimensional conformations. [4]

When the sedimentation coefficient, s, of circular DNA is ascertained over a large range of pH, the following curves are seen. Three curves are shown here, representing three species of DNA. From top-to-bottom they are: "Form IV" (green), "Form I" (blue) and "Form II" (red).

"Form I" (blue curve) is the traditional nomenclature used for the native form of duplex circular DNA, as recovered from viruses and intracellular plasmids. Form I is covalently closed, and any plectonemic winding which may be present is therefore locked in. If one or more nicks are introduced to Form I, free rotation of one strand with respect to the other becomes possible, and Form II (red curve) is seen.

Form IV (green curve) is the product of alkali denaturation of Form I. Its structure is unknown, except that it is persistently duplex, and extremely dense.

Between pH 7 and pH 11.5, the sedimentation coefficient s, for Form I, is constant. Then it dips, and at a pH just below 12, reaches a minimum. With further increases in pH, s then returns to its former value. It doesn't stop there, however, but continues to increase relentlessly. By pH 13, the value of s has risen to nearly 50, two to three times its value at pH 7, indicating an extremely compact structure.

If the pH is then lowered, the s value is not restored. Instead, one sees the upper, green curve. The DNA, now in the state known as Form IV, remains extremely dense, even if the pH is restored to the original physiologic range. As stated previously, the structure of Form IV is almost entirely unknown, and there is no currently accepted explanation for its extraordinary density. About all that is known about the tertiary structure is that it is duplex, but has no hydrogen bonding between bases.

These behaviors of Forms I and IV are considered to be due to the peculiar properties of duplex DNA which has been covalently closed into a double-stranded circle. If the covalent integrity is disrupted by even a single nick in one of the strands, all such topological behavior ceases, and one sees the lower Form II curve (Δ). For Form II, alterations in pH have very little effect on s. Its physical properties are, in general, identical to those of linear DNA. At pH 13, the strands of Form II simply separate, just as the strands of linear DNA do. The separated single strands have slightly different s values, but display no significant changes in s with further increases in pH.

A complete explanation for these data is beyond the scope of this article. In brief, the alterations in s come about because of changes in the superhelicity of circular DNA. These changes in superhelicity are schematically illustrated by four little drawings which have been strategically superimposed upon the figure above.

Briefly, the alterations of s seen in the pH titration curve above are widely thought to be due to changes in the superhelical winding of DNA under conditions of increasing pH. Up to pH 11.5, the purported "underwinding" produces a right-handed ("negative") supertwist. But as the pH increases, and the secondary helical structure begins to denature and unwind, the chromosome (if we may speak anthropomorphically) no longer "wants" to have the full Watson–Crick winding, but rather "wants", increasingly, to be "underwound". Since there is less and less strain to be relieved by superhelical winding, the superhelices therefore progressively disappear as the pH increases. At a pH just below 12, all incentive for superhelicity has expired, and the chromosome will appear as a relaxed, open circle.

At higher pH still, the chromosome, which is now denaturing in earnest, tends to unwind entirely, which it cannot do so (because Lk is covalently locked in). Under these conditions, what was once treated as "underwinding" has actually now become "overwinding". Once again there is strain, and once again it is (in part at least) relieved by superhelicity, but this time in the opposite direction (i.e., left-handed or "positive"). Each left-handed tertiary supertwist removes a single, now undesirable right-handed Watson–Crick secondary twist.

The titration ends at pH 13, where Form IV appears.

See also

Related Research Articles

<span class="mw-page-title-main">DNA</span> Molecule that carries genetic information

Deoxyribonucleic acid is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries 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.

DNA topoisomerases are enzymes that catalyze changes in the topological state of DNA, interconverting relaxed and supercoiled forms, linked (catenated) and unlinked species, and knotted and unknotted DNA. Topological issues in DNA arise due to the intertwined nature of its double-helical structure, which, for example, can lead to overwinding of the DNA duplex during DNA replication and transcription. If left unchanged, this torsion would eventually stop the DNA or RNA polymerases involved in these processes from continuing along the DNA helix. A second topological challenge results from the linking or tangling of DNA during replication. Left unresolved, links between replicated DNA will impede cell division. The DNA topoisomerases prevent and correct these types of topological problems. They do this by binding to DNA and cutting the sugar-phosphate backbone of either one or both of the DNA strands. This transient break allows the DNA to be untangled or unwound, and, at the end of these processes, the DNA backbone is resealed. Since the overall chemical composition and connectivity of the DNA do not change, the DNA substrate and product are chemical isomers, differing only in their topology.

In a chain-like biological molecule, such as a protein or nucleic acid, a structural motif is a common three-dimensional structure that appears in a variety of different, evolutionarily unrelated molecules. A structural motif does not have to be associated with a sequence motif; it can be represented by different and completely unrelated sequences in different proteins or RNA.

<span class="mw-page-title-main">Nucleoid</span> Region within a prokaryotic cell containing genetic material

The nucleoid is an irregularly shaped region within the prokaryotic cell that contains all or most of the genetic material. The chromosome of a typical prokaryote is circular, and its length is very large compared to the cell dimensions, so it needs to be compacted in order to fit. In contrast to the nucleus of a eukaryotic cell, it is not surrounded by a nuclear membrane. Instead, the nucleoid forms by condensation and functional arrangement with the help of chromosomal architectural proteins and RNA molecules as well as DNA supercoiling. The length of a genome widely varies and a cell may contain multiple copies of it.

<span class="mw-page-title-main">Z-DNA</span> One of many possible double helical structures of DNA

Z-DNA is one of the many possible double helical structures of DNA. It is a left-handed double helical structure in which the helix winds to the left in a zigzag pattern, instead of to the right, like the more common B-DNA form. Z-DNA is thought to be one of three biologically active double-helical structures along with A-DNA and B-DNA.

DNA gyrase, or simply gyrase, is an enzyme within the class of topoisomerase and is a subclass of Type II topoisomerases that reduces topological strain in an ATP dependent manner while double-stranded DNA is being unwound by elongating RNA-polymerase or by helicase in front of the progressing replication fork. It is the only known enzyme to actively contribute negative supercoiling to DNA, while it also is capable of relaxing positive supercoils. It does so by looping the template to form a crossing, then cutting one of the double helices and passing the other through it before releasing the break, changing the linking number by two in each enzymatic step. This process occurs in bacteria, whose single circular DNA is cut by DNA gyrase and the two ends are then twisted around each other to form supercoils. Gyrase is also found in eukaryotic plastids: it has been found in the apicoplast of the malarial parasite Plasmodium falciparum and in chloroplasts of several plants. Bacterial DNA gyrase is the target of many antibiotics, including nalidixic acid, novobiocin, albicidin, and ciprofloxacin.

<span class="mw-page-title-main">Superhelix</span>

A superhelix is a molecular structure in which a helix is itself coiled into a helix. This is significant to both proteins and genetic material, such as overwound circular DNA.

<span class="mw-page-title-main">Triple-stranded DNA</span> DNA structure

Triple-stranded DNA is a DNA structure in which three oligonucleotides wind around each other and form a triple helix. In triple-stranded DNA, the third strand binds to a B-form DNA double helix by forming Hoogsteen base pairs or reversed Hoogsteen hydrogen bonds.

<span class="mw-page-title-main">Nucleic acid double helix</span> Structure formed by double-stranded molecules

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 structure was discovered by Rosalind Franklin, her student Raymond Gosling, James Watson, and Francis Crick, while the term "double helix" entered popular culture with the 1968 publication of Watson's The Double Helix: A Personal Account of the Discovery of the Structure of DNA.

Topoisomerase IV is one of two Type II topoisomerases in bacteria, the other being DNA gyrase. Like gyrase, topoisomerase IV is able to pass one double-strand of DNA through another double-strand of DNA, thereby changing the linking number of DNA by two in each enzymatic step. Both share a hetero-4-mer structure formed by a symmetric homodimer of A/B heterodimers, usually named ParC and ParE.

<span class="mw-page-title-main">Type I topoisomerase</span> Class of enzymes

In molecular biology Type I topoisomerases are enzymes that cut one of the two strands of double-stranded DNA, relax the strand, and reanneal the strand. They are further subdivided into two structurally and mechanistically distinct topoisomerases: type IA and type IB.

<span class="mw-page-title-main">Type II topoisomerase</span>

Type II topoisomerases are topoisomerases that cut both strands of the DNA helix simultaneously in order to manage DNA tangles and supercoils. They use the hydrolysis of ATP, unlike Type I topoisomerase. In this process, these enzymes change the linking number of circular DNA by ±2. Topoisomerases are ubiquitous enzymes, found in all living organisms.

<span class="mw-page-title-main">Solenoid (DNA)</span>

The solenoid structure of chromatin is a model for the structure of the 30 nm fibre. It is a secondary chromatin structure which helps to package eukaryotic DNA into the nucleus.

<span class="mw-page-title-main">Netropsin</span> Chemical compound

Netropsin is a polyamide with antibiotic and antiviral activity. Netropsin was discovered by Finlay et al., and first isolated from the actinobacterium Streptomyces netropsis. It belongs to the class of pyrrole-amidine antibiotics.

<span class="mw-page-title-main">Molecular models of DNA</span>

Molecular models of DNA structures are representations of the molecular geometry and topology of deoxyribonucleic acid (DNA) molecules using one of several means, with the aim of simplifying and presenting the essential, physical and chemical, properties of DNA molecular structures either in vivo or in vitro. These representations include closely packed spheres made of plastic, metal wires for skeletal models, graphic computations and animations by computers, artistic rendering. Computer molecular models also allow animations and molecular dynamics simulations that are very important for understanding how DNA functions in vivo.

<span class="mw-page-title-main">Nucleic acid structure</span> Biomolecular structure of nucleic acids such as DNA and RNA

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.

<span class="mw-page-title-main">Obsolete models of DNA structure</span>

In addition to the variety of verified DNA structures, there have been a range of proposed DNA models that have either been disproven, or lack evidence.

<span class="mw-page-title-main">Cruciform DNA</span>

Cruciform DNA is a form of non-B DNA, or an alternative DNA structure. The formation of cruciform DNA requires the presence of palindromes called inverted repeat sequences. These inverted repeats contain a sequence of DNA in one strand that is repeated in the opposite direction on the other strand. As a result, inverted repeats are self-complementary and can give rise to structures such as hairpins and cruciforms. Cruciform DNA structures require at least a six nucleotide sequence of inverted repeats to form a structure consisting of a stem, branch point and loop in the shape of a cruciform, stabilized by negative DNA supercoiling.

<span class="mw-page-title-main">Reverse gyrase</span>

Reverse gyrase is a type I topoisomerase that introduces positive supercoils into DNA, contrary to the typical negative supercoils introduced by the type II topoisomerase DNA gyrase. These positive supercoils can be introduced to DNA that is either negatively supercoiled or fully relaxed. Where DNA gyrase forms a tetramer and is capable of cleaving a double-stranded region of DNA, reverse gyrase can only cleave single stranded DNA. More specifically, reverse gyrase is a member of the type IA topoisomerase class; along with the ability to relax negatively or positively supercoiled DNA, type IA enzymes also tend to have RNA-topoisomerase activities. These RNA topoisomerases help keep longer RNA strands from becoming tangled in what are referred to as "pseudoknots." Due to their ability to interact with RNA, it is thought that this is one of the most ancient class of enzymes found to date.

Non-B DNA refers to DNA conformations that differ from the canonical B-DNA conformation, the most common form of DNA found in nature at neutral pH and physiological salt concentrations. Non-B DNA structures can arise due to various factors, including DNA sequence, length, supercoiling, and environmental conditions. Non-B DNA structures can have important biological roles, but they can also cause problems, such as genomic instability and disease.

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Further reading

  • Bloomfield VA, Crothers DM, Tinoco Jr I (2000). Nucleic acids: structures, properties, and functions. Sausalito, California: University Science Books. pp. 446–453. ISBN   978-0935702491.