Studies Of DNA Mismatch Repair

Environmental Health Sciences

Investigators

Linked publications & trials

Abstract

This year we had five accomplishments. (1) We investigated the interaction of two essential mismatch mismatch repair proteins that form a heterodimer. We used mass spectrometry to identify putative residues involved in the protein-protein interactions and proposed a new model for the interaction surface. (2) We demonstrated that 5-amino-salicylic acid, a chemotherapeutic agent used to treat inflammatory bowel disease, affects cell cycle progression in colorectal cells by reversibly activating a replication checkpoint. (3) We demonstrated that of a specific glutamate (E339) in the Phe-X-Glu motif of yeast Msh6 has a particularly important role in repairing base-base mismatches characteristic of oxidative stress. (4) We demonstrated that the amino-terminal region of yeast Msh6 binds to DNA and provided evidence that this binding is important for MMR in vivo. (5) We performed experiments indicating that exonuclease 1, which participates in the excision step of MMR, is also important for cellular responses to DNA damage induced by environmental agents.