1. Biochemistry and Chemical Biology
  2. Cancer Biology
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Novel RNA and DNA strand exchange activity of the PALB2 DNA Binding Domain and its critical role for DNA repair in cells

  1. Jaigeeth Deveryshetty
  2. Thibaut Peterlini
  3. Mikhail Ryzhikov
  4. Nadine Brahiti
  5. Graham Dellaire
  6. Jean-Yves Masson
  7. Sergey Korolev  Is a corresponding author
  1. Saint Louis University School of Medicine, United States
  2. CHU de Québec-Université Laval, Canada
  3. Dalhousie University, Canada
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Cite this article as: eLife 2019;8:e44063 doi: 10.7554/eLife.44063

Abstract

BReast Cancer Associated proteins 1 and 2 (BRCA1, -2) and Partner and Localizer of BRCA2 (PALB2) protein are tumor suppressors linked to a spectrum of malignancies, including breast cancer and Fanconi anemia. PALB2 coordinates functions of BRCA1 and BRCA2 during homology-directed repair (HDR) and interacts with several chromatin proteins. In addition to protein scaffold function, PALB2 binds DNA. The functional role of this interaction is poorly understood. We identified a major DNA-binding site of PALB2, mutations in which reduce RAD51 foci formation and the overall HDR efficiency in cells by 50%. PALB2 N-terminal DNA-binding domain (N-DBD) stimulates the function of RAD51 recombinase. Surprisingly, it possesses the strand exchange activity without RAD51. Moreover, N-DBD stimulates the inverse strand exchange and can use DNA and RNA substrates. Our data reveal a versatile DNA interaction property of PALB2 and demonstrate a critical role of PALB2 DNA binding for chromosome repair in cells.

Article and author information

Author details

  1. Jaigeeth Deveryshetty

    Edward A Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Thibaut Peterlini

    Genome Stability Laboratory, CHU de Québec-Université Laval, Québec City, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Mikhail Ryzhikov

    Edward A Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Nadine Brahiti

    Genome Stability Laboratory, CHU de Québec-Université Laval, Québec City, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Graham Dellaire

    Department of Pathology, Dalhousie University, Halifax, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3466-6316
  6. Jean-Yves Masson

    Genome Stability Laboratory, CHU de Québec-Université Laval, Québec City, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Sergey Korolev

    Edward A Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St Louis, United States
    For correspondence
    korolevs@slu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9313-7126

Funding

Siteman Cancer Center

  • Sergey Korolev

Foundation for Barnes-Jewish Hospital

  • Sergey Korolev

Canadian Institutes of Health Research

  • Jean-Yves Masson

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

Reviewing Editor

  1. Maria Spies, University of Iowa, United States

Publication history

  1. Received: December 1, 2018
  2. Accepted: April 23, 2019
  3. Accepted Manuscript published: April 24, 2019 (version 1)
  4. Accepted Manuscript updated: April 29, 2019 (version 2)
  5. Version of Record published: May 23, 2019 (version 3)

Copyright

© 2019, Deveryshetty 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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