MSH6 siRNA (Mouse)

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.

Protein type: DNA-binding

Cellular Component: nucleoplasm; Golgi apparatus; intracellular membrane-bound organelle; nuclear chromatin; cytoplasm; plasma membrane; MutSalpha complex; chromosome; intracellular; nucleus

Molecular Function: DNA-dependent ATPase activity; single base insertion or deletion binding; single thymine insertion binding; ATPase activity; oxidized purine DNA binding; nucleotide binding; magnesium ion binding; ADP binding; methylated histone residue binding; mismatched DNA binding; four-way junction DNA binding; DNA binding; single guanine insertion binding; guanine/thymine mispair binding; double-stranded DNA binding; damaged DNA binding; MutLalpha complex binding; chromatin binding; ATP binding

Biological 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 DNA damage stimulus; response to UV