Mechanisms in Eukaryotic Mismatch Repair

Inactivation of the human mismatch repair system confers a large increase in spontaneous mutability and a strong predisposition to tumor development. Mismatch repair provides several genetic stabilization functions; it corrects DNA biosynthetic errors, ensures the fidelity of genetic recombination, and participates in the earliest steps of checkpoint and apoptotic responses to several classes of DNA damage (see Refs. 1–3 for recent reviews). Defects in this pathway are the cause of typical and atypical hereditary nonpolyposis colon cancer (4) but may also play a role in the development of 15–25% of sporadic tumors that occur in a number of tissues (5).