DNA mismatch repair and cancer.
Five human DNA mismatch repair genes have been identified that, when mutated, cause susceptibility to hereditary nonpolyposis colorectal cancer (HNPCC). Mutational inactivation of both copies of a DNA mismatch repair gene results 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 from postreplication repair, DNA mismatch repair proteins have several other functions that are highly relevant to carcinogenesis. These include DNA damage surveillance, prevention of recombination between nonidentical sequences and participation in meiotic processes (chromosome pairing). A brief overview of these different features of the human DNA mismatch repair system will be provided, with the emphasis in their implications in cancer development.
Division of Human Cancer Genetics, Comprehensive Cancer Center, The Ohio State University, 690 Medical Research Facility, 420 W. 12th Avenue, Columbus, OH 43210, USA. peltomaki-1@medctr.osu.edu
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Peltomäki
D000818:Animals; D020137:Base Pair Mismatch / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D004260:DNA Repair / Q000235:genetics*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D051379:Mice; D018895:Microsatellite Repeats / Q000235:genetics; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D011379:Prognosis