Studies Of DNA Mismatch Repair

National Institute Of Environmental Health Sciences

Investigators

Linked publications, trials & patents

Abstract

This year, we published a comprehensive SnapShot of DNA mismatch repair that is intended to be a brief, up-to-date and easy to use reference for students and for investigators in this field. We also made substantial progress in our research on the two aspects of eukaryotic DNA mismatch repair. (1) We investigated the ability of yeast Pms1, an essential mismatch repair protein, to bind to DNA. This ability is required for the essential endonuclease activity of the Mlh1-Pms1 protein complex. This investigation involved a collaboration to solve the crystal structure of the Pms1 N-terminal domain, followed by genetic and biochemical experiments to map the surface of Pms1 that interacts with DNA. (2) We participated in continuing collaborations to investigate the roles of MutS alpha and exonuclease 1 in DNA mismatch repair in mice. This included publication of the characterization of an Msh2-conditional knockout mouse model for studying intestinal cancer and for testing anticancer agents. (3) We also continued intensive (unpublished) experiments aimed at determining the efficiency with which mismatches made during leading and lagging strand DNA replication in yeast are repaired.