1. Chromosomes and Gene Expression
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Multiple kinases inhibit origin licensing and helicase activation to ensure reductive cell division during meiosis

  1. David V Phizicky
  2. Luke E Berchowitz
  3. Stephen P Bell  Is a corresponding author
  1. Massachusetts Institute of Technology, United States
  2. Columbia University Medical Center, United States
Research Article
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Cite this article as: eLife 2018;7:e33309 doi: 10.7554/eLife.33309

Abstract

Meiotic cells undergo a single round of DNA replication followed by two rounds of chromosome segregation (the meiotic divisions) to produce haploid gametes. Both DNA replication and chromosome segregation are similarly regulated by CDK oscillations in mitotic cells. Yet how these two events are uncoupled between the meiotic divisions is unclear. Using Saccharomyces cerevisiae, we show that meiotic cells inhibit both helicase loading and helicase activation to prevent DNA replication between the meiotic divisions. CDK and the meiosis‑specific kinase Ime2 cooperatively inhibit helicase loading, and their simultaneous inhibition allows inappropriate helicase reloading. Further analysis uncovered two previously unknown mechanisms by which Ime2 inhibits helicase loading. Finally, we show that CDK and the polo‑like kinase Cdc5 trigger degradation of Sld2, an essential helicase‑activation protein. Together, our data demonstrate that multiple kinases inhibit both helicase loading and activation between the meiotic divisions, thereby ensuring reductive cell division.

Article and author information

Author details

  1. David V Phizicky

    Department of Biology, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Luke E Berchowitz

    Department of Genetics and Development, Columbia University Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Stephen P Bell

    Department of Biology, Massachusetts Institute of Technology, Cambridge, United States
    For correspondence
    spbell@mit.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2876-610X

Funding

Howard Hughes Medical Institute (Investigator Award)

  • Stephen P Bell

National Cancer Institute (Biopolymer Facility Support)

  • Stephen P Bell

National Institute of General Medical Sciences (Gradaute Student Fellowship)

  • David V Phizicky

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

Reviewing Editor

  1. Bruce Stillman, Cold Spring Harbor Laboratory, United States

Publication history

  1. Received: November 3, 2017
  2. Accepted: January 31, 2018
  3. Accepted Manuscript published: February 1, 2018 (version 1)
  4. Version of Record published: February 8, 2018 (version 2)

Copyright

© 2018, Phizicky 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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