Non-homologous End-joining
Non-homologous end joining (NHEJ) is a pathway that repairs double-strand breaks in DNA. It is called "non-homologous" because the break ends are directly ligated without the need for a homologous template, in contrast to homology directed repair (HDR), which requires a homologous sequence to guide repair. NHEJ is active in both non-dividing and proliferating cells, while HDR is not readily accessible in non-dividing cells. The term "non-homologous end joining" was coined in 1996 by Moore and Haber. NHEJ is typically guided by short homologous DNA sequences called microhomologies. These microhomologies are often present in single-stranded overhangs on the ends of double-strand breaks. When the overhangs are perfectly compatible, NHEJ usually repairs the break accurately. Imprecise repair leading to loss of nucleotides can also occur, but is much more common when the overhangs are not compatible. Inappropriate NHEJ can lead to translocations and telomere fusion, hallmarks of tum ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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LigD
LigD is a multifunctional ligase/polymerase/nuclease ( 3'-phosphoesterase) found in bacterial non-homologous end joining (NHEJ) DNA repair systems. It is much more error-prone than the more complex eukaryotic system of NHEJ, which uses multiple enzymes to fill its role. The polymerase preferentially use rNTPs (RNA nucleotides), possibly advantageous in dormant cells. The actual architecture of LigD is variable. * The LigD homolog in ''Bacillus subtilis ''Bacillus subtilis'' (), known also as the hay bacillus or grass bacillus, is a gram-positive, catalase-positive bacterium, found in soil and the gastrointestinal tract of ruminants, humans and marine sponges. As a member of the genus ''Bacill ...'' does not have the nuclease domain. * LigD with its ligase domain artificially removed can perform its function (with loss of fidelity) with a separate LigC acting as the ligase. * The ''LigD'' homolog in the archaeon ''Methanocella paludicola'' is broken into three single-domain prot ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Yeast
Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom (biology), kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitute 1% of all described fungal species. Some yeast species have the ability to develop multicellular characteristics by forming strings of connected budding cells known as pseudohyphae or false hyphae, or quickly evolve into a Multicellular organism, multicellular cluster with specialised Organelle, cell organelles function. Yeast sizes vary greatly, depending on species and environment, typically measuring 3–4 micrometre, μm in diameter, although some yeasts can grow to 40 μm in size. Most yeasts reproduce asexual reproduction, asexually by mitosis, and many do so by the asymmetric division process known as budding. With their single-celled growth habit, yeasts can be contrasted with Mold (fungus), molds, wh ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Ku80
Ku80 is a protein that, in humans, is encoded by the ''XRCC5'' gene. Together, Ku70 and Ku80 make up the Ku heterodimer, which binds to DNA double-strand break ends and is required for the non-homologous end joining (NHEJ) pathway of DNA repair. It is also required for V(D)J recombination, which utilizes the NHEJ pathway to promote antigen diversity in the mammalian immune system. In addition to its role in NHEJ, Ku is required for telomere length maintenance and subtelomeric gene silencing. Ku was originally identified when patients with systemic lupus erythematosus were found to have high levels of autoantibodies to the protein. Nomenclature Ku80 has been referred to by several names including: * Lupus Ku autoantigen protein p80 * ATP-dependent DNA helicase 2 subunit 2 * X-ray repair complementing defective repair in Chinese hamster cells 5 * X-ray repair cross-complementing 5 (XRCC5) Epigenetic repression The protein expression level of Ku80 can be repressed by e ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Ku70
Ku70 is a heterodimeric protein made up of Ku70 and Ku80, which together form Ku. In humans, is encoded by the ''XRCC6'' gene. Ku70 plays a critical role in the DNA repair, maintenance and many other cellular processes. Function Together, Ku70 and Ku80 make up the Ku heterodimer form a quasi-symmetric structure, which encircles the double-stranded DNA. The DNA double-strand break ends and is required for the non-homologous end joining (NHEJ) of the DNA repair pathway. It is also required for V(D)J recombination, which utilizes the NHEJ pathway to promote antigen diversity in the mammalian immune system. Ku70 is key for sensing and responding to cytosolic DNA, which is essential for the indication of infection. Within the heterodimer, Ku70 specifically binds directly to broken ends of double-stranded DNA breaks, or DSBs. Then together, Ku70 and Ku80 will tightly form a ring-like structure around the DNA strand, preventing further degradation. These steps are essential for the ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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DNA-PKcs
DNA-dependent protein kinase catalytic subunit, also known as DNA-PKcs, is an enzyme that plays a crucial role in repairing DNA double-strand breaks and has a number of other DNA housekeeping functions. In humans it 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 consisting of a single polypeptide chain of 4,128 amino acids. Function DNA-PKcs is the catalytic subunit of a nuclear DNA-dependent serine/threonine protein kinase called DNA-PK. The second component is the autoimmune antigen Ku. On its own, DNA-PKcs is inactive and relies on Ku to direct it to DNA ends and trigger its kinase activity. DNA-PKcs is required for the non-homologous end joining (NHEJ) pathway of DNA repair, which rejoins double-strand breaks. It is also required for V(D)J recombination, a process that utilizes NHEJ to promote immune system diversit ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Mre11-Rad50-Nbs1
The MRN complex (MRX complex in yeast) is a protein complex consisting of MRE11A, Mre11, Rad50 and Nbs1 (also known as Nibrin in humans and as Xrs2 in yeast). In eukaryotes, the MRN/X complex plays an important role in the initial processing of DNA repair, double-strand DNA breaks prior to repair by homologous recombination or non-homologous end joining. The MRN complex binds avidly to double-strand breaks both in vitro and in vivo and may serve to tether broken ends prior to repair by non-homologous end joining or to initiate DNA end resection prior to repair by homologous recombination. The MRN complex also participates in activating the checkpoint kinase Ataxia telangiectasia mutated, ATM in response to DNA damage. Production of short single-strand oligonucleotides by Mre11 endonuclease activity has been implicated in ATM activation by the MRN complex. Evolutionary ancestry and biologic function The MRN complex has been mainly studied in eukaryotes. However, recent work shows ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Nbs1
Nibrin, also known as NBN or NBS1, is a protein which in humans is encoded by the ''NBN'' gene. Function Nibrin is a protein associated with the repair of double strand breaks (DSBs) which pose serious damage to a genome. It is a 754 amino acid protein identified as a member of the NBS1/hMre11/RAD50(N/M/R, more commonly referred to as MRN) double strand DNA break repair complex. This complex recognizes DNA damage and rapidly relocates to DSB sites and forms nuclear foci. It also has a role in regulation of N/M/R (MRN) protein complex activity which includes end-processing of both physiological and mutagenic DNA double strand breaks (DSBs). Cellular response to DSBs Cellular response is performed by damage sensors, effectors of lesion repair and signal transduction. The central role is carried out by ataxia telangiectasia mutated (ATM) by activating the DSB signaling cascade, phosphorylating downstream substrates such as histone H2AX and NBS1. NBS1 relocates to DSB sit ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Mammal
A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three Evolution of mammalian auditory ossicles, middle ear bones. These characteristics distinguish them from reptiles and birds, from which their ancestors Genetic divergence, diverged in the Carboniferous Period over 300 million years ago. Around 6,640 Neontology#Extant taxon, extant species of mammals have been described and divided into 27 Order (biology), orders. The study of mammals is called mammalogy. The largest orders of mammals, by number of species, are the rodents, bats, and eulipotyphlans (including hedgehogs, Mole (animal), moles and shrews). The next three are the primates (including humans, monkeys and lemurs), the Artiodactyl, even-toed ungulates (including pigs, camels, and whales), and the Carnivora (including Felidae, ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Mre11-Rad50-Xrs2
The MRX complex is a heterotrimeric protein complex consisting of Mre11, Rad50, and Xrs2. It is a budding yeast homolog of the mammalian Mre11-Rad50-Nbs1 (MRN) DNA damage repair complex. Double-strand break repair Cells are able to accurately repair DNA double-strand breaks using a process called homologous recombination. By this process DNA sequence information that is lost because of the breakage can be recovered from a second homologous DNA molecule. Homologous recombinational repair is important for removing DNA damage both during mitosis and meiosis. The repair process begins with the degradation of the 5’ end on either side of the double-strand break to yield 3’ single-stranded DNA tails (a process called end resection). Next the Rad51 protein binds to these tails and initiates a process of strand invasion leading to recovery of genetic information from the undamaged homologous sequence of the second DNA molecule. Studies with the yeast ''Saccharomyces cerevisiae ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metabolic reactions, DNA replication, Cell signaling, responding to stimuli, providing Cytoskeleton, structure to cells and Fibrous protein, organisms, and Intracellular transport, transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the Nucleic acid sequence, nucleotide sequence of their genes, and which usually results in protein folding into a specific Protein structure, 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called pep ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Prokaryote
A prokaryote (; less commonly spelled procaryote) is a unicellular organism, single-celled organism whose cell (biology), cell lacks a cell nucleus, nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Ancient Greek (), meaning 'before', and (), meaning 'nut' or 'kernel'. In the earlier two-empire system arising from the work of Édouard Chatton, prokaryotes were classified within the empire Prokaryota. However, in the three-domain system, based upon molecular phylogenetics, prokaryotes are divided into two domain (biology), domains: Bacteria and Archaea. A third domain, Eukaryote, Eukaryota, consists of organisms with nuclei. Prokaryotes evolution, evolved before eukaryotes, and lack nuclei, mitochondria, and most of the other distinct organelles that characterize the eukaryotic cell. Some unicellular prokaryotes, such as cyanobacteria, form colony (biology), colonies held together by biofilms, and large colonies can create multilayered microbial ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |