Rif1 inhibits replication fork progression and controls DNA copy number in Drosophila

  1. Alex Munden
  2. Zhan Rong
  3. Amanda Sun
  4. Rama Gangula
  5. Simon Mallal
  6. Jared T Nordman  Is a corresponding author
  1. Vanderbilt University, United States

Abstract

Control of DNA copy number is essential to maintain genome stability and ensure proper cell and tissue function. In Drosophila polyploid cells, the SNF2-domain-containing SUUR protein inhibits replication fork progression within specific regions of the genome to promote DNA underreplication. While dissecting the function of SUUR's SNF2 domain, we identified an interaction between SUUR and Rif1. Rif1 has many roles in DNA metabolism and regulates the replication timing program. We demonstrate that repression of DNA replication is dependent on Rif1. Rif1 localizes to active replication forks in a partially SUUR-dependent manner and directly regulates replication fork progression. Importantly, SUUR associates with replication forks in the absence of Rif1, indicating that Rif1 acts downstream of SUUR to inhibit fork progression. Our findings uncover an unrecognized function of the Rif1 protein as a regulator of replication fork progression.

Data availability

Sequencing data have been deposited in GEO under accession code GSE114370

The following data sets were generated

Article and author information

Author details

  1. Alex Munden

    Department of Biological Sciences, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Zhan Rong

    Department of Biological Sciences, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Amanda Sun

    Department of Biological Sciences, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Rama Gangula

    Department of Medicine, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Simon Mallal

    Department of Medicine, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jared T Nordman

    Department of Biological Sciences, Vanderbilt University, Nashville, United States
    For correspondence
    jared.nordman@vanderbilt.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6612-3201

Funding

National Institutes of Health (5R00GM104151)

  • Jared T Nordman

National Institutes of Health (P30 AI110527)

  • Simon Mallal

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: June 12, 2018
  2. Accepted: October 1, 2018
  3. Accepted Manuscript published: October 2, 2018 (version 1)
  4. Version of Record published: October 12, 2018 (version 2)

Copyright

© 2018, Munden 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. Alex Munden
  2. Zhan Rong
  3. Amanda Sun
  4. Rama Gangula
  5. Simon Mallal
  6. Jared T Nordman
(2018)
Rif1 inhibits replication fork progression and controls DNA copy number in Drosophila
eLife 7:e39140.
https://doi.org/10.7554/eLife.39140
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