Mutation of MSH3 in endometrial cancer and evidence for its functional role in heteroduplex repair.

摘要: Many human tumours have length alterations in repetitive sequence elements1. Although this microsatellite instability has been attributed to mutations four DNA mismatch repair genes hereditary nonpolyposis colorectal cancer (HNPCC) kindreds2,3, many sporadic exhibit but no detectable these genes4–6. It is therefore of interest identify other that contribute instability. In yeast, several genes, including RTH and MSH3, cause instability7–11. Thus, we screened 16 endometrial carcinomas with for FEN1 (the homolog RTH) MSH3 (refs 12–14). found mutations, a frameshift mutation was observed an carcinoma cell line. Extracts the line were deficient substrates containing mismatches or extra nucleotides. Introducing chromosome 5, encoding gene, into mutant increased stability some not all microsatellites. cells repaired certain nucleotides, those A subsequent search revealed second gene HHUA cells, missense MSH6 gene. Together data suggest encodes product functions pre-mutational intermediates, its can result genomic and, as are partially redundant repair.