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Nonhomologous End Joining
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(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, hallmark ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
V(D)J Recombination
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. V(D)J recombination in mammals occurs in the primary lymphoid organs (bone marrow for B cells and thymus for T cells) and in a nearly random fashion rearranges variable (V), joining (J), and in some cases, diversity (D) gene segments. The process ultimately results in novel amino acid sequences in the antigen-binding regions of immunoglobulins and TCRs that allow for the recognition of antigens from nearly all pathogens including bacteria, viruses, parasites, and worms as well as "altered self cells" as seen in cancer. The recognition can also be allergic in nature (''e.g.'' to pollen or other allergens) or may match ho ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
XLF Protein
Non-homologous end-joining factor 1 (NHEJ1), also known as Cernunnos or XRCC4-like factor (XLF), is a protein that in humans is encoded by the NHEJ1 gene. XLF was originally discovered as the protein mutated in five patients with growth retardation, microcephaly, and immunodeficiency. The protein is required for the non-homologous end joining (NHEJ) pathway of DNA repair. Patients with XLF mutations also have immunodeficiency due to a defect in V(D)J recombination, which uses NHEJ to generate diversity in the antibody repertoire of the immune system. XLF interacts with DNA ligase IV and XRCC4 and is thought to be involved in the end-bridging or ligation steps of NHEJ. The yeast (''Saccharomyces cerevisiae'') homolog of XLF is Nej1. Phenotypes In contrast to the profound immunodeficiency phenotype of XLF deletion in humans, deletion of XLF alone has a mild phenotype in mice. However, combining a deletion of XLF with deletion of the ATM kinase causes a synthetic defect in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Yeast
Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus 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. Yeasts are unicellular organisms that evolved from multicellular ancestors, with some species having the ability to develop multicellular characteristics by forming strings of connected budding cells known as pseudohyphae or false hyphae. Yeast sizes vary greatly, depending on species and environment, typically measuring 3–4 µm in diameter, although some yeasts can grow to 40 µm in size. Most yeasts reproduce 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 molds, which grow hyphae. Fungal species that can take both forms (depending on temperature or other conditions) are ca ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 epig ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ku70
Ku70 is a protein that, in humans, is encoded by the ''XRCC6'' gene. Function 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 also 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. Aging Mouse embryonic stem cells with homozygous Ku70 mutations, that is Ku70−/− cells, have markedly increased sensitivity to ionizing radiation compared to heterozygous Ku70+/− or wild-type Ku70+/+ embryonic stem cells. Mutant mice deficient in Ku70 exhibit early aging. Using several specific criteria of aging, the mutant m ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
DNA-PKcs
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. 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 diversity. DNA-PKcs knockout mice have severe combined immunodeficiency due to their V(D)J recombination defect. Many proteins ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mre11-Rad50-Nbs1
The MRN complex (MRX complex in yeast) is a protein complex consisting of 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 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 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 that two of the three protein components of this ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 sites ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mammal
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or hair, and three middle ear bones. These characteristics distinguish them from reptiles (including birds) from which they diverged in the Carboniferous, over 300 million years ago. Around 6,400 extant species of mammals have been described divided into 29 orders. The largest orders, in terms of number of species, are the rodents, bats, and Eulipotyphla (hedgehogs, moles, shrews, and others). The next three are the Primates (including humans, apes, monkeys, and others), the Artiodactyla ( cetaceans and even-toed ungulates), and the Carnivora (cats, dogs, seals, and others). In terms of cladistics, which reflects evolutionary history, mammals are the only living members of the Synapsida (synapsids); this clade, together with Saur ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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] |
