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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 most essential part for biological inheritance. This is essential for cell division during growth and repair of damaged tissues, while it also ensures that each of the new cells receives its own copy of the DNA. The cell possesses the distinctive property of division, which makes replication of DNA essential.
Protein engineering is the process of developing useful or valuable proteins. It is a young discipline, with much research taking place into the understanding of protein folding and recognition for protein design principles. It is also a product and services market, with an estimated value of $168 billion by 2017.
A nuclease is an enzyme capable of cleaving the phosphodiester bonds between nucleotides of nucleic acids. Nucleases variously affect single and double stranded breaks in their target molecules. In living organisms, they are essential machinery for many aspects of DNA repair. Defects in certain nucleases can cause genetic instability or immunodeficiency. Nucleases are also extensively used in molecular cloning.
In genetics, a transcription terminator is a section of nucleic acid sequence that marks the end of a gene or operon in genomic DNA during transcription. This sequence mediates transcriptional termination by providing signals in the newly synthesized transcript RNA that trigger processes which release the transcript RNA from the transcriptional complex. These processes include the direct interaction of the mRNA secondary structure with the complex and/or the indirect activities of recruited termination factors. Release of the transcriptional complex frees RNA polymerase and related transcriptional machinery to begin transcription of new mRNAs.
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA damage, resulting in tens of thousands of individual molecular lesions per cell per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur, including double-strand breaks and DNA crosslinkages. This can eventually lead to malignant tumors, or cancer as per the two hit hypothesis.
RecQ helicase is a family of helicase enzymes initially found in Escherichia coli that has been shown to be important in genome maintenance. They function through catalyzing the reaction ATP + H2O → ADP + P and thus driving the unwinding of paired DNA and translocating in the 3' to 5' direction. These enzymes can also drive the reaction NTP + H2O → NDP + P to drive the unwinding of either DNA or RNA.
Non-homologous end joining (NHEJ) is a pathway that repairs double-strand breaks in DNA. NHEJ is referred to as "non-homologous" because the break ends are directly ligated without the need for a homologous template, in contrast to homology directed repair, which requires a homologous sequence to guide repair. The term "non-homologous end joining" was coined in 1996 by Moore and Haber.
This is a list of topics in molecular biology. See also index of biochemistry articles.
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids. It is widely used by cells to accurately repair harmful breaks that occur on both strands of DNA, known as double-strand breaks (DSB), in a process called homologous recombinational repair (HRR). Homologous recombination also produces new combinations of DNA sequences during meiosis, the process by which eukaryotes make gamete cells, like sperm and egg cells in animals. These new combinations of DNA represent genetic variation in offspring, which in turn enables populations to adapt during the course of evolution. Homologous recombination is also used in horizontal gene transfer to exchange genetic material between different strains and species of bacteria and viruses.
Terminal deoxynucleotidyl transferase (TdT), also known as DNA nucleotidylexotransferase (DNTT) or terminal transferase, is a specialized DNA polymerase expressed in immature, pre-B, pre-T lymphoid cells, and acute lymphoblastic leukemia/lymphoma cells. TdT adds N-nucleotides to the V, D, and J exons of the TCR and BCR genes during antibody gene recombination, enabling the phenomenon of junctional diversity. In humans, terminal transferase is encoded by the DNTT gene. As a member of the X family of DNA polymerase enzymes, it works in conjunction with polymerase λ and polymerase μ, both of which belong to the same X family of polymerase enzymes. The diversity introduced by TdT has played an important role in the evolution of the vertebrate immune system, significantly increasing the variety of antigen receptors that a cell is equipped with to fight pathogens. Studies using TdT knockout mice have found drastic reductions (10-fold) in T-cell receptor (TCR) diversity compared with that of normal, or wild-type, systems. The greater diversity of TCRs that an organism is equipped with leads to greater resistance to infection. Although TdT was one of the first DNA polymerases identified in mammals in 1960, it remains one of the least understood of all DNA polymerases. In 2016–18, TdT was discovered to demonstrate in trans template dependant behaviour in addition to its more broadly known template independent behaviour
V(D)J recombination is the mechanism of somatic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation. It results in the highly diverse repertoire of antibodies/immunoglobulins and T cell receptors (TCRs) found in B cells and T cells, respectively. The process is a defining feature of the adaptive immune system.
The replisome is a complex molecular machine that carries out replication of DNA. The replisome first unwinds double stranded DNA into two single strands. For each of the resulting single strands, a new complementary sequence of DNA is synthesized. The Total result is formation of two new double stranded DNA sequences that are exact copies of the original double stranded DNA sequence.
The recombination-activating genes (RAGs) encode parts of a protein complex that plays important roles in the rearrangement and recombination of the genes encoding immunoglobulin and T cell receptor molecules. There are two recombination-activating genes RAG1 and RAG2, whose cellular expression is restricted to lymphocytes during their developmental stages. The enzymes encoded by these genes, RAG-1 and RAG-2, are essential to the generation of mature B cells and T cells, two types of lymphocyte that are crucial components of the adaptive immune system.
DNA repair protein XRCC4 also known as X-ray repair cross-complementing protein 4 or XRCC4 is a protein that in humans is encoded by the XRCC4 gene. In addition to humans, the XRCC4 protein is also expressed in many other metazoans, fungi and in plants. The X-ray repair cross-complementing protein 4 is one of several core proteins involved in the non-homologous end joining (NHEJ) pathway to repair DNA double strand breaks (DSBs).
DNA-dependent protein kinase, catalytic subunit, also known as DNA-PKcs, is an enzyme that in humans is encoded by the gene designated as PRKDC or XRCC7. DNA-PKcs belongs to the phosphatidylinositol 3-kinase-related kinase protein family. The DNA-Pkcs protein is a serine/threonine protein kinase comprising a single polypeptide chain of 4,128 amino acids.
Artemis is a protein that in humans is encoded by the DCLRE1C gene.
Junctional diversity describes the DNA sequence variations introduced by the improper joining of gene segments during the process of V(D)J recombination. This process of V(D)J recombination has vital roles for the vertebrate immune system, as it is able to generate a huge repertoire of different T-cell receptor (TCR) and immunoglobulin molecules required for pathogen antigen recognition by T-cells and B cells, respectively.
Recombination signal sequences are conserved sequences of noncoding DNA that are recognized by the RAG1/RAG2 enzyme complex during V(D)J recombination in immature B cells and T cells. Recombination signal sequences guide the enzyme complex to the V, D, and J gene segments that will undergo recombination during the formation of the heavy and light-chain variable regions in T-cell receptors and immunoglobulin molecules.
DNA end resection, also called 5′–3′ degradation, is a biochemical process where the blunt end of a section of double-stranded DNA (dsDNA) is modified by cutting away some nucleotides from the 5' end to produce a 3' single-stranded sequence. The presence of a section of single-stranded DNA (ssDNA) allows the broken end of the DNA to line up accurately with a matching sequence, so that it can be accurately repaired.
Rolling hairpin replication (RHR) is a unidirectional, strand displacement form of DNA replication used by parvoviruses, a group of viruses that constitute the family Parvoviridae. Parvoviruses have linear, single-stranded DNA (ssDNA) genomes in which the coding portion of the genome is flanked by telomeres at each end that form hairpin loops. During RHR, these hairpin loops repeatedly unfold and refold to change the direction of DNA replication so that replication progresses in a continuous manner back and forth across the genome. RHR is initiated and terminated by an endonuclease encoded by parvoviruses that is variously called NS1 or Rep, and RHR is similar to rolling circle replication, which is used by ssDNA viruses that have circular genomes.
References
- ↑ Ma, Y; Pannicke, U; Schwarz, K; Lieber, MR (2002). "Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination". Cell. 108 (6): 781–94. doi: 10.1016/S0092-8674(02)00671-2 . PMID 11955432.