MSH2 is a key mammalian DNA mismatch repair (MMR) gene and mutations or deficiencies in mammalian Msh2 gene result in microsatellite instability (MSI+) and the development of cancer [PMID: 16331258]. Mismatch repair (MMR) proteins is a group of nuclear enzymes, which in all proliferating cells participate in repair of base-base mismatch, that occur during DNA replication. The proteins form complexes (heterodimers) that bind to areas of abnormal DNA and initiates its removal. Loss of MMR proteins leads to an accumulation of DNA replication errors in the proliferating cells, particularly in areas of the genome with short repetitive nucleotide sequences, a phenomenon known as microsatellite instability (MSI). In human, nine genes with MMR function have been identified. More than 300 different mutations have been identified. Persons carrying a mutation have normal MMR proteins, but in case of a DNA damage involving the nonmutated allel, the protein production stops (loss of heterozygosity). When forming complexes MLH1 heterodimerizes with PMS2, PMS1 or MLH3 (another MMR protein, for which a mutation has not been detected), while MSH2 heterodimerizes with MSH6. In case of MSH2 deficiency, MSH6 protein is also lost, possibly because of protein instability.
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