Mitotic crossovers between diverged sequences are regulated by mismatch repair proteins in Saccaromyces cerevisiae

Author:

Datta A1,Adjiri A1,New L1,Crouse G F1,Jinks Robertson S1

Affiliation:

1. Graduate Program in Biochemistry and Molecular Biology, Emory University, Atlanta, Georgia 30322, USA.

Abstract

Mismatch repair systems correct replication- and recombination-associated mispaired bases and influence the stability of simple repeats. These systems thus serve multiple roles in maintaining genetic stability in eukaryotes, and human mismatch repair defects have been associated with hereditary predisposition to cancer. In prokaryotes, mismatch repair systems also have been shown to limit recombination between diverged (homologous) sequences. We have developed a unique intron-based assay system to examine the effects of yeast mismatch repair genes (PMS1, MSH2, and MSH3) on crossovers between homologous sequences. We find that the apparent antirecombination effects of mismatch repair proteins in mitosis are related to the degree of substrate divergence. Defects in mismatch repair can elevate homologous recombination between 91% homologous substrates as much as 100-fold while having only modest effects on recombination between 77% homologous substrates. These observations have implications for genome stability and general mechanisms of recombination in eukaryotes.

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

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