MSH2 Antibody

This locus is frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). When cloned, it was discovered to be a human homolog of the E. coli mismatch repair gene mutS, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in HNPCC. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

MSH2: Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2- MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. 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. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis. Heterodimer consisting of MSH2-MSH6 (MutS alpha) or MSH2- MSH3 (MutS beta). Both heterodimer form a ternary complex with MutL alpha (MLH1-PMS1). Interacts with EXO1. Part of the BRCA1- associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with ATR. Interacts with SLX4/BTBD12; this interaction is direct and links MutS beta to SLX4, a subunit of different structure-specific endonucleases. Interacts with SMARCAD1. Ubiquitously expressed. Belongs to the DNA mismatch repair MutS family.

Protein type: DNA-binding; Tumor suppressor

Chromosomal Location of Human Ortholog: 2p21

Cellular Component: nucleoplasm; nuclear chromosome; membrane; MutSalpha complex; MutSbeta complex

Molecular Function: protein C-terminus binding; DNA-dependent ATPase activity; double-strand/single-strand DNA junction binding; protein homodimerization activity; dinucleotide repeat insertion binding; single thymine insertion binding; ATPase activity; oxidized purine DNA binding; magnesium ion binding; ADP binding; protein kinase binding; mismatched DNA binding; loop DNA binding; centromeric DNA binding; Y-form DNA binding; protein binding; enzyme binding; four-way junction DNA binding; DNA binding; single guanine insertion binding; double-stranded DNA binding; guanine/thymine mispair binding; MutLalpha complex binding; dinucleotide insertion or deletion binding; single-stranded DNA binding; ATP binding

Biological Process: determination of adult life span; maintenance of DNA repeat elements; germ cell development; positive regulation of helicase activity; double-strand break repair; negative regulation of neuron apoptosis; cell cycle arrest; DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis; response to X-ray; oxidative phosphorylation; negative regulation of DNA recombination; mismatch repair; postreplication repair; in utero embryonic development; male gonad development; somatic hypermutation of immunoglobulin genes; isotype switching; DNA repair; response to UV-B; meiotic mismatch repair; B cell mediated immunity; intra-S DNA damage checkpoint; B cell differentiation; meiotic gene conversion; somatic recombination of immunoglobulin gene segments; negative regulation of meiotic recombination

Disease: Muir-torre Syndrome; Mismatch Repair Cancer Syndrome; Lynch Syndrome I