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

  1. Nicholas Chim
  2. Lynnette N Jackson
  3. Anh M Trinh
  4. John C Chaput  Is a corresponding author
  1. University of California, Irvine, United States

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.

Data availability

Coordinates and structure factors have been deposited in the PDB with the accession codes: 6DSU, 6DSV, 6DSW, 6DSX, and 6DSY.

The following data sets were generated

Article and author information

Author details

  1. Nicholas Chim

    Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2274-5305
  2. Lynnette N Jackson

    Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Anh M Trinh

    Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. John C Chaput

    Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, United States
    For correspondence
    jchaput@uci.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1393-135X

Funding

Defense Advanced Research Projects Agency (N66001-16-2-4061)

  • John C Chaput

National Science Foundation (1607111)

  • John C Chaput

National Institutes of Health (R25GM055246)

  • Lynnette N Jackson

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. John Kuriyan, University of California, Berkeley, United States

Publication history

  1. Received: July 25, 2018
  2. Accepted: October 18, 2018
  3. Accepted Manuscript published: October 19, 2018 (version 1)
  4. Version of Record published: November 12, 2018 (version 2)

Copyright

© 2018, Chim et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Nicholas Chim
  2. Lynnette N Jackson
  3. Anh M Trinh
  4. John C Chaput
(2018)
Crystal structures of DNA polymerase I capture novel intermediates in the DNA synthesis pathway
eLife 7:e40444.
https://doi.org/10.7554/eLife.40444
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