Crystal structures of DNA polymerase I capture novel intermediates in the DNA synthesis pathway

Author:

Chim Nicholas1ORCID,Jackson Lynnette N1,Trinh Anh M1,Chaput John C123ORCID

Affiliation:

1. Departments of Pharmaceutical Sciences, University of California, Irvine, California

2. Department of Chemistry, University of California, Irvine, California

3. Department of Molecular Biology and Biochemistry, University of California, Irvine, California

Abstract

High resolution crystal structures of DNA polymerase intermediates are needed to study the mechanism of DNA synthesis in cells. Here we report five crystal structures of DNA polymerase I that capture new conformations for the polymerase translocation and nucleotide pre-insertion steps in the DNA synthesis pathway. We suggest that these new structures, along with previously solved structures, highlight the dynamic nature of the finger subdomain in the enzyme active site.

Funder

Defense Advanced Research Projects Agency

National Science Foundation

National Institutes of Health

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Reference22 articles.

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3. A mutant of DNA polymerase I (Klenow fragment) with reduced fidelity;Carroll;Biochemistry,1991

4. MolProbity: all-atom structure validation for macromolecular crystallography;Chen;Acta Crystallographica Section D Biological Crystallography,2010

5. The PyMOL Molecular Graphics System;Delano,2002

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