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  • interacts
  • We report that MSH2 (MutS homolog 2) protein interacts with the ATR (ATM- and Rad3-related) kinase to form a signaling module and regulate the phosphorylation of Chk1 and SMC1 (structure maintenance of chromosome 1). (pnas.org)
  • We found that MSH2 protein interacts with the ATR kinase constitutively to form a signaling module that regulates the phosphorylation of downstream effectors including Chk1 and SMC1 (structure maintenance of chromosome 1). (pnas.org)
  • The crystal structure of MutS reveals that it is exceptionally asymmetric, and, while its active conformation is a dimer, only one of the two halves interacts with the mismatch site. (wikipedia.org)
  • ATPase
  • The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. (uniprot.org)
  • As with other MutS homologs, hMSH6 has an intrinsic ATPase activity. (wikipedia.org)
  • It has been proposed that histone proteins are evolutionarily related to the helical part of the extended AAA+ ATPase domain, the C-domain, and to the N-terminal substrate recognition domain of Clp/Hsp100 proteins. (wikipedia.org)
  • tumor
  • 1 , 2 If this function is lost in a cell due to MUTYH mutation of both alleles, there are increased G:C→T:A transversions (a guanine-cytosine pair to a thymine-adenine pair) 2 in other genes including tumor suppressors, which could increase cancer risk. (pubmedcentralcanada.ca)
  • MSI was determined by polymerase chain reaction/fragment analysis and MSH2 protein expression by immunohistochemistry on retrieved tumor tissue. (ox.ac.uk)
  • These interactions form protein complexes that are typically involved in tumor suppression and DNA repair activities. (wikipedia.org)
  • Immunohistochemistry
  • Evidence indicating microsatellite stability in three of 17 patients with a clinical history indicative of Muir-Torre syndrome and a mutation in only MSH-6 suggests that the phenotype of a germline MSH-6 mutation differs from that of MLH-1 and MSH-2 mutations and further supports the use of immunohistochemistry as a screening tool in patients with Muir-Torre syndrome with an extended panel that includes MSH-6. (umassmed.edu)
  • METHODS: Using immunohistochemistry, tumour expression of 2 MMR genes, hMLH1 and hMSH2, was assessed in 86 patients with advanced CRC, who were treated with either irinotecan alone or in combination with 5-flurouracil/folinic acid. (ox.ac.uk)
  • MSH5
  • These findings in mouse and human indicate that the MSH5 protein plays an important role in meiotic recombination. (wikipedia.org)
  • In the worm Caenorhabditis elegans, the MSH5 protein is required during meiosis both for normal spontaneous and for gamma-irradiation induced crossover recombination and chiasma formation. (wikipedia.org)
  • signaling pathway
  • We found that phosphorylation of Chk1 by ATR also requires checkpoint proteins Rad17 and replication protein A. In contrast, phosphorylation of SMC1 by ATR is independent of Rad17 and replication protein A, suggesting that the signaling pathway leading to SMC1 phosphorylation is distinct from that mediated by the checkpoint proteins. (pnas.org)
  • Transitional Cell
  • OBJECTIVES: To establish whether high microsatellite instability (MSI) (present in almost 20% of cases) and loss of MSH2 protein expression (sometimes used to predict MSI status) are prognostic factors of overall survival for patients with invasive upper urinary tract transitional cell carcinoma (UUT-TCC). (ox.ac.uk)
  • degradation
  • Phosphorylated by PRKCZ, which may prevent MutS alpha degradation by the ubiquitin-proteasome pathway. (waw.pl)
  • amino acid
  • Computational protein design algorithms seek to identify novel amino acid sequences that are low in energy when folded to the pre-specified target structure. (wikipedia.org)
  • chromosome
  • Chromosome 2 is the second-largest human chromosome, spanning more than 242 million base pairs (the building material of DNA) and representing almost 8% of the total DNA in human cells. (wikipedia.org)
  • Chromosome 2 contains the HOXD homeobox gene cluster. (wikipedia.org)
  • Human chromosome 2 is a result of an end-to-end fusion of two ancestral chromosomes. (wikipedia.org)
  • The evidence for this includes: The correspondence of chromosome 2 to two ape chromosomes. (wikipedia.org)
  • The closest human relative, the chimpanzee, has near-identical DNA sequences to human chromosome 2, but they are found in two separate chromosomes. (wikipedia.org)
  • Normally a chromosome has just one centromere, but in chromosome 2 there are remnants of a second centromere in the q21.3-q22.1 region. (wikipedia.org)
  • These are normally found only at the ends of a chromosome, but in chromosome 2 there are additional telomere sequences in the q13 band, far from either end of the chromosome. (wikipedia.org)
  • According to researcher J. W. IJdo, "We conclude that the locus cloned in cosmids c8.1 and c29B is the relic of an ancient telomere-telomere fusion and marks the point at which two ancestral ape chromosomes fused to give rise to human chromosome 2. (wikipedia.org)
  • The following are some of the gene count estimates of human chromosome 2. (wikipedia.org)
  • See also: Category:Genes on human chromosome 2. (wikipedia.org)
  • The following is a partial list of genes on human chromosome 2. (wikipedia.org)
  • In the human genome, hMSH6 is located on chromosome 2. (wikipedia.org)
  • The human microRNA-21 gene is located on plus strand of chromosome 17q23.2 (55273409-55273480) within a coding gene TMEM49 (also called vacuole membrane protein). (wikipedia.org)
  • recognizes
  • MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. (uniprot.org)
  • double stranded
  • The MutSα dimer scans double stranded DNA in the nucleus, looking for mismatched bases. (wikipedia.org)
  • While the exact criteria as defined in the scientific literature vary, giant viruses are generally described as viruses having large pseudo-icosahedral capsids (200 to 400 nanometers) which can be surrounded by a thick (approximately 100 nm) layer of filamentous protein fibers with large double-stranded DNA genomes (300 to 1000 kilobase pairs or larger) encoding a large contingent of genes (of the order of 1000 genes). (wikipedia.org)
  • deletion loops
  • This dimer repairs longer insertion/deletion loops than MutSα. (wikipedia.org)
  • MutSα is responsible for base-base mispairs and short insertion/deletion loops, while MutSβ reapirs long insertion/deletion loops in DNA. (wikipedia.org)
  • While both proteins have redundant function in base-base repairs, MutSα typically effects base-base mispair repairs and also performs repairs on the more common short inertion/deletion loops. (wikipedia.org)
  • MutSβ can compensate somewhat for loss of base-base mispair correction functions, but is not suited for repairing many short, 1-2 base pair insertion/deletion loops. (wikipedia.org)
  • sequences
  • While the sequence-conformation space that needs to be searched is large, the most challenging requirement for computational protein design is a fast, yet accurate, energy function that can distinguish optimal sequences from similar suboptimal ones. (wikipedia.org)
  • These techniques involve alignment of target protein sequences with other related protein sequences. (wikipedia.org)
  • Multiple sequence alignment utilizes data bases such as PREFAB, SABMARK, OXBENCH, IRMBASE, and BALIBASE in order to cross reference target protein sequences with known sequences. (wikipedia.org)
  • sequence
  • Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed. (uniprot.org)
  • They were the first to perform "exomic sequencing", meaning determination of the sequence of every protein-encoding gene in the human genome. (wikipedia.org)
  • The 4 'core' histones (H2A, H2B, H3 and H4) are relatively similar in structure and are highly conserved through evolution, all featuring a 'helix turn helix turn helix' motif (DNA-binding protein motif that recognize specific DNA sequence). (wikipedia.org)
  • Without structural information about a protein, sequence analysis is often useful in elucidating information about the protein. (wikipedia.org)
  • interactions
  • In the case of endonucleases such as EcoRV, BamHI, and PvuII, this nonspecific binding involves electrostatic interactions between minimal surface area of the protein and the DNA. (wikipedia.org)
  • complexes
  • Crossing over and DNA repair are very similar processes, which utilize many of the same protein complexes. (wikipedia.org)
  • A drastic shift in the relative levels of these protein complexes can lead to diminished capacity for MMR. (wikipedia.org)
  • chromatin
  • Using a murine model of inflammation-induced tumorigenesis, we tested the hypothesis that inflammation promotes recruitment of epigenetic proteins to chromatin, initiating methylation and gene silencing in tumors. (aacrjournals.org)
  • They are the chief protein components of chromatin, acting as spools around which DNA winds, and playing a role in gene regulation. (wikipedia.org)
  • evolutionarily
  • It down-regulates BCL6 (B-cell lymphoma 6) protein [ 8 ], which is an evolutionarily conserved zinc finger transcription factor that contains an N-terminal POZ/BTB domain. (biomedcentral.com)
  • nicks
  • Recent work has shown that nicks are sites for RFC-dependent loading of the replication sliding clamp PCNA, in an orientation-specific manner, such that one face of the donut-shape protein is juxtaposed toward the 3'-OH end at the nick. (wikipedia.org)
  • Upon activation by the MutS-DNA complex, MutH nicks the daughter strand near the hemimethylated site. (wikipedia.org)
  • Outcome
  • The presence of EMAST was not related to tumour grade, stage, subsequent outcome or immunohistochemical expression of the MMR proteins. (ox.ac.uk)
  • replication
  • One mechanism of DNA damage recognition has been elucidated recently, in which binding of replication protein A (RPA) to single-stranded DNA (ssDNA) results in recruitment of the ATR-interacting protein ATRIP to load the ATR/ATRIP complex to ssDNA, leading to activation of ATR ( 4 ). (pnas.org)
  • Proliferating cell nuclear antigen (PCNA) is a protein involved in post-replication MMR. (wikipedia.org)
  • Bound PCNA then localizes the MutSβ complex to replication foci, indicating that PCNA assists in initiating repair by guiding MutSβ and other repair proteins to free termini in recently replicated DNA. (wikipedia.org)
  • form
  • Duchenne Muscular Dystrophy (DMD) is an X-linked genetic disorder that results in the production of a dysfunctional form of the protein, dystrophin. (nih.gov)
  • yeast
  • Genetic work from yeast has established the current conceptual framework of DNA damage response ( 2 ). (pnas.org)
  • recombinase
  • We also report that the frequency of genetic repair of the mdx mutation can be enhanced if RNAi is used to suppress expression of the recombinase inhibitor protein Msh2 in cultures containing myoblasts but not in those heavily enriched in myoblasts. (nih.gov)
  • One such particular protein complex that is conserved between processes is RAD51, a well conserved recombinase protein that has been shown to be crucial in DNA repair as well as cross over. (wikipedia.org)
  • alterations
  • Loss of MutS homolog 2 (MSH2), a mismatch repair (MMR) protein, abrogated early inflammation-induced epigenetic alterations and DNA hypermethylation alterations observed in inflammation-induced tumors. (aacrjournals.org)
  • These results indicate that early epigenetic alterations initiated by inflammation and MMR proteins lead to gene silencing during tumorigenesis, revealing a novel mechanism of epigenetic alterations in inflammation-driven cancer. (aacrjournals.org)
  • tumors
  • In contrast, γδ-T cells bearing the Vδ2 gene with the co-expression of the Vγ9 chain (Vγ9Vδ2-T cells) are abundant in the peripheral blood and lymphoid organs of most healthy individuals, and they are involved in the first line of the immune responses to mycobacteria, Epstein-Barr virus (EBV), and some solid tumors ( 1 , 2 , 4 - 10 ). (frontiersin.org)
  • double stranded
  • The MutSα dimer scans double stranded DNA in the nucleus, looking for mismatched bases. (wikipedia.org)
  • Meiotic recombination may be initiated by double-stranded breaks that are introduced into the DNA by exposure to DNA damaging agents or the Spo11 protein. (wikipedia.org)
  • While the exact criteria as defined in the scientific literature vary, giant viruses are generally described as viruses having large pseudo-icosahedral capsids (200 to 400 nanometers) which can be surrounded by a thick (approximately 100 nm) layer of filamentous protein fibers with large double-stranded DNA genomes (300 to 1000 kilobase pairs or larger) encoding a large contingent of genes (of the order of 1000 genes). (wikipedia.org)
  • amino
  • Computational protein design algorithms seek to identify novel amino acid sequences that are low in energy when folded to the pre-specified target structure. (wikipedia.org)
  • This alignment can show which amino acids are conserved between species and are important for the function of the protein. (wikipedia.org)
  • chromosome
  • Chromosome 2 is one of the 23 pairs of chromosomes in humans. (wikipedia.org)
  • Chromosome 2 is the second-largest human chromosome, spanning more than 242 million base pairs (the building material of DNA) and representing almost 8% of the total DNA in human cells. (wikipedia.org)
  • Chromosome 2 contains the HOXD homeobox gene cluster. (wikipedia.org)
  • Human chromosome 2 is a result of an end-to-end fusion of two ancestral chromosomes. (wikipedia.org)
  • The evidence for this includes: The correspondence of chromosome 2 to two ape chromosomes. (wikipedia.org)
  • The closest human relative, the chimpanzee, has near-identical DNA sequences to human chromosome 2, but they are found in two separate chromosomes. (wikipedia.org)
  • Normally a chromosome has just one centromere, but in chromosome 2 there are remnants of a second centromere in the q21.3-q22.1 region. (wikipedia.org)
  • These are normally found only at the ends of a chromosome, but in chromosome 2 there are additional telomere sequences in the q13 band, far from either end of the chromosome. (wikipedia.org)
  • According to researcher J. W. IJdo, "We conclude that the locus cloned in cosmids c8.1 and c29B is the relic of an ancient telomere-telomere fusion and marks the point at which two ancestral ape chromosomes fused to give rise to human chromosome 2. (wikipedia.org)
  • The following are some of the gene count estimates of human chromosome 2. (wikipedia.org)
  • See also: Category:Genes on human chromosome 2. (wikipedia.org)
  • The following is a partial list of genes on human chromosome 2. (wikipedia.org)
  • The human microRNA-21 gene is located on plus strand of chromosome 17q23.2 (55273409-55273480) within a coding gene TMEM49 (also called vacuole membrane protein). (wikipedia.org)
  • DNA mismatch repair protein Msh2 also known as MutS protein homolog 2 or MSH2 is a protein that in humans is encoded by the MSH2 gene, which is located on chromosome 2. (wikipedia.org)
  • interactions
  • In the case of endonucleases such as EcoRV, BamHI, and PvuII, this nonspecific binding involves electrostatic interactions between minimal surface area of the protein and the DNA. (wikipedia.org)
  • During mitosis and meiosis, the condensed chromosomes are assembled through interactions between nucleosomes and other regulatory proteins. (wikipedia.org)
  • deletion
  • This dimer repairs longer insertion/deletion loops than MutSα. (wikipedia.org)
  • MutSα is responsible for base-base mispairs and short insertion/deletion loops, while MutSβ reapirs long insertion/deletion loops in DNA. (wikipedia.org)
  • While both proteins have redundant function in base-base repairs, MutSα typically effects base-base mispair repairs and also performs repairs on the more common short inertion/deletion loops. (wikipedia.org)
  • MutSβ can compensate somewhat for loss of base-base mispair correction functions, but is not suited for repairing many short, 1-2 base pair insertion/deletion loops. (wikipedia.org)
  • histones
  • In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. (wikipedia.org)
  • The 4 'core' histones (H2A, H2B, H3 and H4) are relatively similar in structure and are highly conserved through evolution, all featuring a 'helix turn helix turn helix' motif (DNA-binding protein motif that recognize specific DNA sequence). (wikipedia.org)
  • nicks
  • Recent work has shown that nicks are sites for RFC-dependent loading of the replication sliding clamp PCNA, in an orientation-specific manner, such that one face of the donut-shape protein is juxtaposed toward the 3'-OH end at the nick. (wikipedia.org)
  • Upon activation by the MutS-DNA complex, MutH nicks the daughter strand near the hemimethylated site. (wikipedia.org)
  • Sequence
  • While the sequence-conformation space that needs to be searched is large, the most challenging requirement for computational protein design is a fast, yet accurate, energy function that can distinguish optimal sequences from similar suboptimal ones. (wikipedia.org)
  • Without structural information about a protein, sequence analysis is often useful in elucidating information about the protein. (wikipedia.org)
  • Multiple sequence alignment utilizes data bases such as PREFAB, SABMARK, OXBENCH, IRMBASE, and BALIBASE in order to cross reference target protein sequences with known sequences. (wikipedia.org)
  • They were the first to perform "exomic sequencing", meaning determination of the sequence of every protein-encoding gene in the human genome. (wikipedia.org)
  • replication
  • Following the completion of graduate training in 1973, Tom spent 2 years as a Jane Coffins Child postdoctoral fellow with Don Williamson at the National Institute for Medical Research in London, where he continued to study DNA replication in yeast. (genetics.org)
  • Proliferating cell nuclear antigen (PCNA) is a protein involved in post-replication MMR. (wikipedia.org)
  • Bound PCNA then localizes the MutSβ complex to replication foci, indicating that PCNA assists in initiating repair by guiding MutSβ and other repair proteins to free termini in recently replicated DNA. (wikipedia.org)
  • complex
  • While much has been learned from previous binding studies of MutS, the contribution of the protein dynamics on MutS complex formation and intra- and inter-domain communication events are not fully resolved at the atomic level. (jbsdonline.com)
  • These chromatids separate to opposite poles, a process facilitated by a protein complex referred to as cohesin. (wikipedia.org)
  • One such particular protein complex that is conserved between processes is RAD51, a well conserved recombinase protein that has been shown to be crucial in DNA repair as well as cross over. (wikipedia.org)
  • PCNA
  • anti_ PCNA antibody, rabbit serum anti_ PCNA antibody, rabbit serum rabbit polyclonal These antibodies are very stable and can be stored up to 2 months at fridge temperature under 10C. (antibody-antibodies.com)
  • Do not freeze taw, rather use anti_ PCNA antibody, rabbit serum anti_ PCNA antibody, rabbit serum from the fridge if your use is less than 1 or 2 weeks. (antibody-antibodies.com)
  • forms
  • Impaired function of these proteins leads to microsatellite instability (MSI) and forms a suitable background for the development and progression of tumors, mainly colorectal cancer. (docplayer.cz)
  • The results for the free and bound forms of the protein are analyzed to determine which model of allostery - conformational pathway, energy landscape or vibrational coupling - best describes the process. (jbsdonline.com)
  • repair
  • Detection methods for microsatellite instability include polymerase chain reaction (PCR) and immunohistochemical (IHC) methods, polymerase chain checking the DNA and immunohistochemical surveying mismatch repair protein levels. (wikipedia.org)
  • Annotation
  • p>An evidence describes the source of an annotation, e.g. an experiment that has been published in the scientific literature, an orthologous protein, a record from another database, etc. (uniprot.org)
  • cancers
  • Of all MSI-H colorectal cancers, 1/5 is caused by Lynch syndrome, the rest being only sporadic cancers caused by epigenetic inactivation of a MMR protein. (docplayer.cz)
  • BRCA1
  • The germline BRCA1 mutation rate in USC subjects of 2% is higher than expected in a nonfounder population, suggesting that USC is associated with hereditary breast and ovarian carcinoma in a small proportion of cases. (uptodate.com)
  • function
  • In the future, more detailed knowledge of protein structure and function, and advances in high-throughput screening, may greatly expand the abilities of protein engineering. (wikipedia.org)
  • In rational protein design, a scientist uses detailed knowledge of the structure and function of a protein to make desired changes. (wikipedia.org)
  • Prior to these studies, the only biochemical function attributed to p53 was its binding to heat shock proteins. (wikipedia.org)