Paul L. Modrich
Duke University
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Primary Section: 21, Biochemistry Membership Type:
Member
(elected 1993)
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Research Interests
Our laboratory studies DNA mismatch repair, which corrects base-pairing errors in the DNA helix and plays an important role in the control of mutation production. We previously identified multiple proteins and enzymes responsible for mismatch repair in both E. coli and human cells and established basic mechanistic features of the pathway in both organisms. During the course of this work, we demonstrated that certain cancers are defective in mismatch repair and identified the components of the repair system that are lacking in these tumor cells. We also showed that mismatch repair-defective cells are resistant to certain anti-cancer drugs. Current work addresses the molecular basis of this drug-resistant phenotype as well as the involvement of mismatch repair in the instability of triplet repeat sequences, the cause of about a dozen neurodegenerative diseases.
