Anti-MSH6, clone MSH6/3085

0.2 mg/ml in 1X PBS with 0.1 mg/ml BSA (US sourced) and 0.05% sodium azide. The finding that mutations in DNA mismatch repair genes are associated with hereditary nonpolyposis colorectal cancer (HNPCC) has resulted in considerable interest in the understanding of the mechanism of DNA mismatch repair. Initially, inherited mutations in the MSH2 and MLH1 homologs of the bacterial DNA mismatch repair genes mutS and mutL were demonstrated at high frequency in HNPCC and were shown to be associated with microsatellite instability. A member of the mismatch repair family, GTBP (also designated MSH6), is an MSH2-related protein that binds to DNA containing G/T mismatches. Findings suggest that the mismatch-binding factor in human cells is composed of a heterodimer of GTBP and MSH2. Protein function: 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. Recruited on chromatin in G1 and early S phase via its PWWP domain that specifically binds trimethylated 'Lys-36' of histone H3 (H3K36me3): early recruitment to chromatin to be replicated allowing a quick identification of mismatch repair to initiate the DNA mismatch repair reaction. [The UniProt Consortium]