DNA-REPAIR AND COLORECTAL-CANCER

The mismatch repair system plays a major role in the processing of rec ombination intermediates and in the repair of errors made during DNA r eplication or resulting from chemical damage to DNA. Human homologues of the bacterial and yeast mismatch repair genes have been recently id entified, and mutations in these genes have been found to show risk fo r tumor development in hereditary nonpolyposis colorectal cancer syndr ome (HNPCC). Colorectal tumors bearing homozygous mutations in these m ismatch repair genes show a hypermutable phenotype, mainly at microsat ellite regions of DNA. The temporal relationship between the loss of m ismatch repair activity and the cascades of mutations in critical gene s involved in the carcinogenesis of HNPCC tumors is unknown.