DNA repair and colorectal cancer

The mismatch repair system plays a major role in the processing of recombination intermediates and in the repair of errors made during DNA replication or resulting from chemical damage to DNA. Human homologues of the bacterial and yeast mismatch repair genes have been recently identified, and mutations in these genes have been found to show risk for tumor development in hereditary nonpolyposis colorectal cancer syndrome (HNPCC). Colorectal tumors bearing homozygous mutations in these mismatch repair genes show a hypermutable phenotype, mainly at microsatellite regions of DNA. The temporal relationship between the loss of mismatch repair activity and the cascades of mutations in critical genes involved in the carcinogenesis of HNPCC tumors is unknown.