DNA MISMATCH REPAIR AND CANCER

Mutations in DNA mismatch repair (MMR) genes have been associated with hereditary nonpolyposis colorectal cancer. Studies in bacteria, yeast and mammals suggest that the basic components of the MMR system are e volutionarily conserved, but studies in eukaryotes also imply novel fu nctions for MMR proteins. Recent results suggest that mutations in MMR genes lead to tumorigenesis in mice, but DNA replication errors appea r to be insufficient to initiate intestinal tumorigenesis in this mode l system. Additionally, MMR-deficient cell lines display a mutator phe notype and resistance to several cytotoxic agents, including compounds widely used in cancer chemotherapy.