DNA mismatch repair and cancer

Five human DNA mismatch repair genes have been identified that, when mutate d, cause susceptibility to hereditary nonpolyposis colorectal cancer (HNPCC ). Mutational inactivation of both copies of a DNA mismatch repair gene res ults in a profound repair defect and progressive accumulation of mutations throughout the genome. Some of the mutations confer selective advantage on the cells, giving rise to cancer. Recent discoveries suggest that apart fro m postreplication repair, DNA mismatch repair proteins have several other f unctions that are highly relevant to carcinogenesis. These include DNA dama ge surveillance, prevention of recombination between nonidentical sequences and participation in meiotic processes (chromosome pairing). A brief overv iew of these different features of the human DNA mismatch repair system wil l be provided, with the emphasis in their implications in cancer developmen t. (C) 2001 Elsevier Science B.V. All rights reserved.