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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] |
Non-homologous 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, hallmarks ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Non-homologous 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, hallmarks ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
DNA Damage Theory Of Aging
The DNA damage theory of aging proposes that aging is a consequence of unrepaired accumulation of naturally occurring DNA damage. Damage in this context is a DNA alteration that has an abnormal structure. Although both mitochondrial and nuclear DNA damage can contribute to aging, nuclear DNA is the main subject of this analysis. Nuclear DNA damage can contribute to aging either indirectly (by increasing apoptosis or cellular senescence) or directly (by increasing cell dysfunction). Several review articles have shown that deficient DNA repair, allowing greater accumulation of DNA damage, causes premature aging; and that increased DNA repair facilitates greater longevity. Mouse models of nucleotide-excision–repair syndromes reveal a striking correlation between the degree to which specific DNA repair pathways are compromised and the severity of accelerated aging, strongly suggesting a causal relationship. Human population studies show that single-nucleotide polymorphisms in D ... [...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] |
Ataxia Telangiectasia Mutated
ATM serine/threonine kinase or Ataxia-telangiectasia mutated, symbol ATM, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. It phosphorylates several key proteins that initiate activation of the DNA damage checkpoint, leading to cell cycle arrest, DNA repair or apoptosis. Several of these targets, including p53, CHK2, BRCA1, NBS1 and H2AX are tumor suppressors. In 1995, the gene was discovered by Yosef Shiloh who named its product ATM since he found that its mutations are responsible for the disorder ataxia–telangiectasia#Cause, ataxia–telangiectasia. In 1998, the Shiloh and Michael B. Kastan, Kastan laboratories independently showed that ATM is a protein kinase whose activity is enhanced by DNA damage. Introduction Throughout the cell cycle DNA is monitored for damage. Damages result from errors during DNA replication, replication, by-products of metabolism, general toxic drugs or ionizing radiation. The cell cycle has diffe ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ataxia Telangiectasia Mutated
ATM serine/threonine kinase or Ataxia-telangiectasia mutated, symbol ATM, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. It phosphorylates several key proteins that initiate activation of the DNA damage checkpoint, leading to cell cycle arrest, DNA repair or apoptosis. Several of these targets, including p53, CHK2, BRCA1, NBS1 and H2AX are tumor suppressors. In 1995, the gene was discovered by Yosef Shiloh who named its product ATM since he found that its mutations are responsible for the disorder ataxia–telangiectasia#Cause, ataxia–telangiectasia. In 1998, the Shiloh and Michael B. Kastan, Kastan laboratories independently showed that ATM is a protein kinase whose activity is enhanced by DNA damage. Introduction Throughout the cell cycle DNA is monitored for damage. Damages result from errors during DNA replication, replication, by-products of metabolism, general toxic drugs or ionizing radiation. The cell cycle has diffe ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phosphatidylinositol 3-kinase-related Kinase
Phosphatidylinositol 3-kinase-related kinases (PIKKs) are a family of Ser/Thr-protein kinases with sequence similarity to phosphatidylinositol-3 kinases ( PI3Ks). Members The human PIKK family includes six members: Structure PIKKs proteins contain the following four domains: # N-terminus FRAP-ATM- TRRAP (FAT) domain, # kinase domain (KD; PI3_PI4_kinase), # PIKK- regulatory domain (PRD), and # C-terminus The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ... FAT-C-terminal (FATC) domain References External links Kinase Family PIKKaWikiKinome EC 2.7.11 Protein families {{protein-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ku (protein)
Ku is a dimeric protein complex that binds to DNA double-strand break ends and is required for the non-homologous end joining (NHEJ) pathway of DNA repair. Ku is evolutionarily conserved from bacteria to humans. The ancestral bacterial Ku is a homodimer (two copies of the same protein bound to each other). Eukaryotic Ku is a heterodimer of two polypeptides, Ku70 (XRCC6) and Ku80 (XRCC5), so named because the molecular weight of the human Ku proteins is around 70 kDa and 80 kDa. The two Ku subunits form a basket-shaped structure that threads onto the DNA end. Once bound, Ku can slide down the DNA strand, allowing more Ku molecules to thread onto the end. In higher eukaryotes, Ku forms a complex with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to form the full DNA-dependent protein kinase, DNA-PK. Ku is thought to function as a molecular scaffold to which other proteins involved in NHEJ can bind, orienting the double-strand break for ligation. The Ku70 and ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CHUK
Inhibitor of nuclear factor kappa-B kinase subunit alpha (IKK-α) also known as IKK1 or conserved helix-loop-helix ubiquitous kinase (CHUK) is a protein kinase that in humans is encoded by the ''CHUK'' gene. IKK-α is part of the IκB kinase complex that plays an important role in regulating the NF-κB transcription factor. However, IKK-α has many additional cellular targets, and is thought to function independently of the NF-κB pathway to regulate epidermal differentiation. Function NF-κB response IKK-α is a member of the serine/threonine protein kinase family and forms a complex in the cell with IKK-β and NEMO. NF-κB transcription factors are normally held in an inactive state by the inhibitory proteins IκBs. IKK-α and IKK-β phosphorylate the IκB proteins, marking them for degradation via ubiquitination and allowing NF-κB transcription factors to go into the nucleus. Once activated, NF-κB transcription factors regulate genes that are implicated in many ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
DNA Repair
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 (interstrand crosslinks or ICLs). This can eventually lead to malignant ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CDC5L
Cell division cycle 5-like protein is a protein that in humans is encoded by the ''CDC5L'' gene. Function The protein encoded by this gene shares a significant similarity with ''Schizosaccharomyces pombe'' cdc5 gene product, which is a cell cycle regulator important for G2/ M transition. This protein has been demonstrated to act as a positive regulator of cell cycle G2/M progression. It was also found to be an essential component of a non-snRNA spliceosome, which contains at least five additional protein factors and is required for the second catalytic step of pre-mRNA splicing. Interactions CDC5L has been shown to interact with: * ASF/SF2, * BZW1, * CWC15, * DNA-PKcs, * DYNC1H1, * GCN1L1, * HSPA8, * ILF2, * PLRG1, * PPM1D, * PPP1CA, * PRPF19, * RBMX and * RPL12, * RPL13, * RPS16, * RPS25, * SF3A1, * SF3B1, * SF3B2, * SF3B4, * SFPQ, * SFRS2, * SNRPA1, * SNRPD3, * SRRM1, * Small nuclear ribonucleoprotein D1, * Small nuclear ribonucleoprotein D2, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. For an average human child between eight and fourteen years old, approximately twenty to thirty billion cells die per day. In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular injury, apoptosis is a highly regulated and controlled process that confers advantages during an organism's life cycle. For example, the separation of fingers and toes in a developing human embryo occurs because cells between the digits undergo apoptosis. Unlike necrosis, apoptosis produces cell fragments called apoptotic ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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