1. Chromosomes and Gene Expression
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RNase H enables efficient repair of R-loop induced DNA damage

  1. Jeremy D Amon
  2. Douglas Koshland  Is a corresponding author
  1. University of California, Berkeley, United States
Research Article
  • Cited 50
  • Views 3,775
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Cite this article as: eLife 2016;5:e20533 doi: 10.7554/eLife.20533

Abstract

R-loops, three-stranded structures that form when transcripts hybridize to chromosomal DNA, are potent agents of genome instability. This instability has been explained by the ability of R-loops to induce DNA damage. Here, we show that persistent R-loops also compromise DNA repair. Depleting endogenous RNase H activity impairs R-loop removal in Saccharomyces cerevisiae, causing DNA damage that occurs preferentially in the repetitive ribosomal DNA locus (rDNA). We analyzed the repair kinetics of this damage and identified mutants that modulate repair. We present a model that the persistence of R-loops at sites of DNA damage induces repair by break-induced replication (BIR). This R-loop induced BIR is particularly susceptible to the formation of lethal repair intermediates at the rDNA because of a barrier imposed by RNA polymerase I.

Article and author information

Author details

  1. Jeremy D Amon

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8748-5228
  2. Douglas Koshland

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    For correspondence
    koshland@berkeley.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3742-6294

Funding

National Institutes of Health (GM092813)

  • Jeremy D Amon
  • Douglas Koshland

National Science Foundation

  • Jeremy D Amon

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

Reviewing Editor

  1. Andrés Aguilera, CABIMER, Universidad de Sevilla, Spain

Publication history

  1. Received: August 10, 2016
  2. Accepted: December 9, 2016
  3. Accepted Manuscript published: December 10, 2016 (version 1)
  4. Version of Record published: January 4, 2017 (version 2)

Copyright

© 2016, Amon & Koshland

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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