DNA mismatch repair and cancer

Abstract

DNA mismatch repair (MMR) is an important genome caretaker system. It ensures genomic stability by correcting mismatches generated during DNA replication and recombination and by triggering apoptosis of cells with large amounts of DNA damage. Protein components responsible for these reactions are highly conserved through evolution, and homologs of bacterial MutS and MutL, which are key players in the initiation steps of both the strand-specific mismatch correction and MMR-dependent apoptotic signaling, have been identified in human cells. Inactivation of genes encoding these activities leads to genome-wide instability, particularly in simple repetitive sequences, and predisposition to certain types of cancer, including hereditary non-polyposis colorectal cancer.