Novel dominant mutations in Saccharomyces cerevisiae MSH6

摘要: Inherited mutations in the mismatch repair (MMR) genes MSH2 and MLH1 are found most hereditary nonpolyposis colon cancer (HNPCC) patients studied1. Eukaryotic MMR uses two partially redundant mispair-recognition complexes, Msh2p–Msh6p Msh2p–Msh3p (ref.2) Inactivation of causes high rates accumulation both base-substitution frameshift mutations. Mutations MSH6 or MSH3 cause partial defects MMR, with inactivation resulting low mutations; results These different mutator phenotypes provide an explanation for observation that common HNPCC families, whereas rare1,3,5. We have identified novel missense Saccharomyces cerevisiae appear to inactivate Msh2p–Msh6p- Msh2p–Msh3p-dependent MMR. Our work suggests such may underlie some cases inherited susceptibility similar those caused by