Molecular Mechanisms Underlying Hereditary Nonpolyposis Colorectal Carcinoma

Abstract

MutS and MutL are bacterial genes that have critical roles in DNA repair and recombination. Mutations in homologues of these genes cause hereditary nonpolyposis colorectal carcinoma and are implicated in some sporadic (nonhereditary) colorectal cancers. Molecular functions of these genes have been defined through extensive work in bacteria and yeast. This article reviews and explores molecular events that require MutS and MutL , including mismatch repair, homologous recombination, and gense conversion. The mechanisms of action of eukaryotic MutS and MutL homologues are compared with those of their prokaryotic counterparts, and the relevance of these mechanisms to tumorigenesis is discussed. [J Natl Cancer Inst 1996;88:240–51]