1. Biochemistry and Chemical Biology
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Characterization of human translesion DNA synthesis across a UV-induced DNA lesion

  1. Mark Hedglin
  2. Binod Pandey
  3. Stephen J Benkovic  Is a corresponding author
  1. The Pennsylvania State University, United States
Research Article
  • Cited 27
  • Views 1,586
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Cite this article as: eLife 2016;5:e19788 doi: 10.7554/eLife.19788

Abstract

Translesion DNA synthesis (TLS) during S-phase uses specialized TLS DNA polymerases to replicate a DNA lesion, allowing stringent DNA synthesis to resume beyond the offending damage. Human TLS involves the conjugation of ubiquitin to PCNA clamps encircling damaged DNA and the role of this post-translational modification is under scrutiny. A widely-accepted model purports that ubiquitinated PCNA recruits TLS polymerases such as pol η to sites of DNA damage where they may also displace a blocked replicative polymerase. We provide extensive quantitative evidence that the binding of pol η to PCNA and the ensuing TLS are both independent of PCNA ubiquitination. Rather, the unique properties of pols η and δ are attuned to promote an efficient and passive exchange of polymerases during TLS on the lagging strand.

Article and author information

Author details

  1. Mark Hedglin

    Department of Chemistry, The Pennsylvania State University, University Park, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Binod Pandey

    Department of Chemistry, The Pennsylvania State University, University Park, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Stephen J Benkovic

    Department of Chemistry, The Pennsylvania State University, University Park, United States
    For correspondence
    sjb1@psu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3680-3481

Funding

National Institutes of Health (GM13306)

  • Stephen J Benkovic

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

Reviewing Editor

  1. Michael R Botchan, University of California, Berkeley, United States

Publication history

  1. Received: July 18, 2016
  2. Accepted: October 21, 2016
  3. Accepted Manuscript published: October 22, 2016 (version 1)
  4. Version of Record published: November 25, 2016 (version 2)

Copyright

© 2016, Hedglin 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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