Strand-specific Mismatch Repair in Mammalian Cells

Abstract

Mistakes occurring during DNA transactions necessarily produce mismatched base pairs. DNA biosynthetic errors that escape the polymerase editing function yield mispaired bases, but mismatches also populate a recombination heteroduplex produced by strand transfer between related sequences that have diverged at the nucleotide level. Study of microbial systems has demonstrated the importance of mismatch correction in the reversal of such errors and consequent stabilization of the genome (1-4).1 Interest in this process has increased dramatically over the past few years with the demonstration that mismatch repair plays an equally important role in mutation avoidance in mammalian cells and the finding that inactivation of the system by inherited or somatic mutation predisposes cells to tumor development and renders them resistant to the cytotoxic effects of certain DNA-damaging agents.