Mistnatch repair and cancer

Abstract DNA mismatch repair is one of the three known DNA excision repair pathways. Unlike nucleotide and base excision repair, in which the substrate is damaged or altered DNA, mismatch repair acts on undamaged DNA bases which are in in appropriate contexts. Mismatch repair corrects unmodified DNA bases in non Watson-Crick pairings or small distortions generated by the incorrect alignment of two otherwise normal DNA strands. Structural abnormalities such as these are generated during recombination between DNA molecules that are not perfectly homologous, and the phrase ‘mismatch repair’ was originally invoked to explain apparently anomalous recombination frequencies. DNA replication errors are also a major source of mismatches. Mismatch repair acts after replication to rectify mismatches that have evaded proofreading by the replication apparatus. Organisms with defective mismatch repair invariably display increased spontaneous mutation rates. Although some of the later steps of the three excision repair pathways share common components, the initial steps, in which the substrate for repair is identified and marked for correction, can be considered unique for each pathway. There is an additional constraint on substrate recognition during mismatch repair. To achieve biologically significant correction, the repair proteins must not only recognize the structurally anomalous mismatches, but must also obtain information as to which of the mispaired DNA strands is incorrect.