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| Name |
Modrich, Paul L. |
| Location
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Duke University Medical Center |
| Primary Field
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Biochemistry |
 Election Citation
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Modrich elucidated the principle and mechanism of repair of mismatched base pairs in DNA arising from errors during replication. His work illustrates beautifully how a seven enzyme Escherichia coli system can preserve the nucleotide sequences of the parental strands while correcting errors in the newly synthesized strands. |
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Research Interests
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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. |
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