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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] |
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 repair#Double-strand breaks, DNA double-strand breaks (Canonical pathway, canonical pathway), oxidative stress, topoisomerase cleavage complexes, splicing intermediates, R-loops and in some cases by DNA repair, single-strand DNA breaks. It phosphorylates several key proteins that initiate activation of the DNA damage cell cycle checkpoint, 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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Rad50
DNA repair protein RAD50, also known as RAD50, is a protein that in humans is encoded by the ''RAD50'' gene. Function The protein encoded by this gene is highly similar to ''Saccharomyces cerevisiae'' Rad50, a protein involved in DNA double-strand break repair. This protein forms a complex with MRE11 and NBS1 (also known as Xrs2 in yeast). This MRN complex (MRX complex in yeast) binds to broken DNA ends and displays numerous enzymatic activities that are required for double-strand break repair by nonhomologous end-joining or homologous recombination. Gene knockout studies of the mouse homolog of Rad50 suggest it is essential for cell growth and viability. Two alternatively spliced transcript variants of Rad50, which encode distinct proteins, have been reported. Structure Rad50 is a member of the structural maintenance of chromosomes (SMC) family of proteins. Like other SMC proteins, Rad50 contains a long internal coiled-coil domain that folds back on itself, bringing t ... [...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 sit ... [...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. 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 t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
P16INK4a
p16 (also known as p16INK4a, cyclin-dependent kinase inhibitor 2A, CDKN2A, multiple tumor suppressor 1 and numerous other synonyms), is a protein that slows cell division by slowing the progression of the cell cycle from the G1 phase to the S phase, thereby acting as a tumor suppressor. It is encoded by the ''CDKN2A'' gene. A deletion (the omission of a part of the DNA sequence during replication) in this gene can result in insufficient or non-functional p16, accelerating the cell cycle and resulting in many types of cancer. p16 can be used as a biomarker to improve the histological diagnostic accuracy of grade 3 cervical intraepithelial neoplasia (CIN). p16 is also implicated in the prevention of melanoma, oropharyngeal squamous cell carcinoma, cervical cancer, vulvar cancer and esophageal cancer. p16 was discovered in 1993. It is a protein with 148 amino acids and a molecular weight of 16 kDa that comprises four ankyrin repeats. The name of p16 is derived from its mo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
T-cell Lymphoma
T-cell lymphoma is a rare form of cancerous lymphoma affecting T cell, T-cells. Lymphoma arises mainly from the uncontrolled proliferation of lymphocytes, such as T-cells, and can become cancerous. T-cell lymphoma is categorized under Non-Hodgkin lymphoma (NHL) and represents less than 15% of all Non-Hodgkin's diseases in the category. T-cell lymphomas are often categorised based on their growth patterns as either aggressive (fast-growing) or indolent (slow-growing). Although the cause of T-cell lymphoma is not definitive, it has been associated with various risk factors and viruses such as Epstein–Barr virus (EBV) and Human T cell leukemia virus-1, human T-cell leukemia virus-1 (HTLV1). The prognosis and treatment of T-cell lymphoma can vary drastically based on the specific type of lymphoma and its growth patterns. Due to their rarity and high variability between the different subtypes, the prognosis of T-cell lymphoma is significantly worse than other Non-Hodgkin lymphoma. Th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MRE11
Double-strand break repair protein MRE11 (Meiotic recombination 11) is an enzyme that in humans is encoded by the ''MRE11'' gene. The gene has been designated ''MRE11A'' to distinguish it from the pseudogene ''MRE11B'' that is nowadays named ''MRE11P1''. Function This gene encodes a nuclear protein involved in homologous recombination, telomere length maintenance, and DNA double-strand break repair. By itself, the protein has 3' to 5' exonuclease activity and endonuclease activity. The protein forms a complex with the RAD50 homolog; this complex is required for nonhomologous joining of DNA ends and possesses increased single-stranded DNA endonuclease and 3' to 5' exonuclease activities. In conjunction with a DNA ligase, this protein promotes the joining of noncomplementary ends in vitro using short homologies near the ends of the DNA fragments. This gene has a pseudogene on chromosome 3. Alternative splicing of this gene results in two transcript variants encoding different is ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
P16INK4a
p16 (also known as p16INK4a, cyclin-dependent kinase inhibitor 2A, CDKN2A, multiple tumor suppressor 1 and numerous other synonyms), is a protein that slows cell division by slowing the progression of the cell cycle from the G1 phase to the S phase, thereby acting as a tumor suppressor. It is encoded by the ''CDKN2A'' gene. A deletion (the omission of a part of the DNA sequence during replication) in this gene can result in insufficient or non-functional p16, accelerating the cell cycle and resulting in many types of cancer. p16 can be used as a biomarker to improve the histological diagnostic accuracy of grade 3 cervical intraepithelial neoplasia (CIN). p16 is also implicated in the prevention of melanoma, oropharyngeal squamous cell carcinoma, cervical cancer, vulvar cancer and esophageal cancer. p16 was discovered in 1993. It is a protein with 148 amino acids and a molecular weight of 16 kDa that comprises four ankyrin repeats. The name of p16 is derived from its mo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
DNA Methylation
DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter (genetics), promoter, DNA methylation typically acts to repress gene Transcription (genetics), transcription. In mammals, DNA methylation is essential for normal development and is associated with a number of key processes including genomic imprinting, X-chromosome inactivation, repression of transposable elements, aging, and carcinogenesis. As of 2016, two nucleobases have been found on which natural, enzymatic DNA methylation takes place: adenine and cytosine. The modified bases are N6-methyladenine,D. B. Dunn, J. D. Smith: "The occurrence of 6-methylaminopurine in deoxyribonucleic acids". In: ''Biochem J.'' 68(4), Apr 1958, S. 627–636. [//www.ncbi.nlm.nih.gov/pubmed/13522672?dopt=Abstract PMID 13522672]. . 5-methylcytosineB. F. Vanyushin, S. G. Tkacheva, A. N. Belozers ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein Complex
A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multidomain enzymes, in which multiple active site, catalytic domains are found in a single polypeptide chain. Protein complexes are a form of protein quaternary structure, quaternary structure. Proteins in a protein complex are linked by non-covalent interactions, non-covalent protein–protein interactions. These complexes are a cornerstone of many (if not most) biological processes. The cell is seen to be composed of modular supramolecular complexes, each of which performs an independent, discrete biological function. Through proximity, the speed and selectivity of binding interactions between Enzyme, enzymatic complex and substrates can be vastly improved, leading to higher cellular efficiency. Many of the techniques used to enter cells and isolate proteins are inherently disruptive to such large complexes, complicating the task of determining ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MCF7
MCF-7 is a breast cancer cell line isolated in 1970 from a 69-year-old woman. MCF-7 is the acronym of Michigan Cancer Foundation-7, referring to the institute in Detroit where the cell line was established in 1973 by Herbert Soule and co-workers. The Michigan Cancer Foundation is now known as the Barbara Ann Karmanos Cancer Institute. Prior to MCF-7, it was not possible for cancer researchers to obtain a mammary cell line that was capable of living longer than a few months. The patient, Frances Mallon died in 1970 due to metastatic breast cancer. Her cells were the source of much of current knowledge about breast cancer. At the time of sampling, she was a nun in the convent of Immaculate Heart of Mary in Monroe, Michigan under the name of Sister Catherine Frances. MCF-7 and two other breast cancer cell lines, named T-47D and MDA-MB-231, account for more than two-thirds of all abstracts reporting studies on mentioned breast cancer cell lines, as concluded from a Medline-based s ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
