MSH6
Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs, and recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. After mismatch binding, 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. Heterodimer consisting of MSH2-MSH6 (MutS alpha). Forms 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. Belongs to the DNA mismatch repair MutS family. 2 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Molecular Function: DNA-dependent ATPase activity; protein homodimerization activity; single thymine insertion binding; oxidized purine DNA binding; ATPase activity; magnesium ion binding; ADP binding; mismatched DNA binding; protein binding; four-way junction DNA binding; single guanine insertion binding; double-stranded DNA binding; guanine/thymine mispair binding; MutLalpha complex binding; chromatin binding; ATP binding
Biological Process: ATP catabolic process; negative regulation of DNA recombination; mismatch repair; somatic hypermutation of immunoglobulin genes; isotype switching; determination of adult life span; DNA repair; maintenance of DNA repeat elements; meiotic mismatch repair; positive regulation of helicase activity; DNA damage response, signal transduction resulting in induction of apoptosis; meiotic recombination; somatic recombination of immunoglobulin gene segments; response to UV
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.
