Kinesin Kif2C in regulation of DNA double strand break dynamics and repair

  1. Songli Zhu
  2. Mohammadjavad Paydar
  3. Feifei Wang
  4. Yanqiu Li
  5. Ling Wang
  6. Benoit Barrette
  7. Tadayoshi Bessho
  8. Benjamin H Kwok  Is a corresponding author
  9. Aimin Peng  Is a corresponding author
  1. University of Nebraska Medical Center, United States
  2. Université de Montréal, Canada

Abstract

DNA double strand breaks (DSBs) have detrimental effects on cell survival and genomic stability, and are related to cancer and other human diseases. In this study, we identified microtubule-depolymerizing kinesin Kif2C as a protein associated with DSB-mimicking DNA templates and known DSB repair proteins in Xenopus egg extracts and mammalian cells. The recruitment of Kif2C to DNA damage sites was dependent on both PARP and ATM activities. Kif2C knockdown or knockout led to accumulation of endogenous DNA damage, DNA damage hypersensitivity, and reduced DSB repair via both NHEJ and HR. Interestingly, Kif2C depletion, or inhibition of its microtubule depolymerase activity, reduced the mobility of DSBs, impaired the formation of DNA damage foci, and decreased the occurrence of foci fusion and resolution. Taken together, our study established Kif2C as a new player of the DNA damage response, and presented a new mechanism that governs DSB dynamics and repair.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Songli Zhu

    Department of Oral Biology, University of Nebraska Medical Center, Lincoln, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Mohammadjavad Paydar

    Institute for Research in Immunology and Cancer, Département de médecine, Université de Montréal, Montréal, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0569-7017
  3. Feifei Wang

    Department of Oral Biology, University of Nebraska Medical Center, Lincoln, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Yanqiu Li

    Department of Oral Biology, University of Nebraska Medical Center, Lincoln, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Ling Wang

    Department of Oral Biology, University of Nebraska Medical Center, Lincoln, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Benoit Barrette

    Institute for Research in Immunology and Cancer, Département de médecine, Université de Montréal, Montréal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Tadayoshi Bessho

    Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Lincoln, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8719-9646
  8. Benjamin H Kwok

    Institute for Research in Immunology and Cancer, Département de médecine, Université de Montréal, Montréal, Canada
    For correspondence
    benjamin.kwok@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
  9. Aimin Peng

    Department of Oral Biology, University of Nebraska Medical Center, Lincoln, United States
    For correspondence
    aimin.peng@unmc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2452-1949

Funding

National Institutes of Health (CA172574)

  • Aimin Peng

Canadian Institutes of Health Research (148982)

  • Benjamin H Kwok

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

Reviewing Editor

  1. Wolf-Dietrich Heyer, University of California, Davis, United States

Version history

  1. Received: November 7, 2019
  2. Accepted: January 16, 2020
  3. Accepted Manuscript published: January 17, 2020 (version 1)
  4. Accepted Manuscript updated: January 21, 2020 (version 2)
  5. Version of Record published: February 11, 2020 (version 3)

Copyright

© 2020, Zhu 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. Songli Zhu
  2. Mohammadjavad Paydar
  3. Feifei Wang
  4. Yanqiu Li
  5. Ling Wang
  6. Benoit Barrette
  7. Tadayoshi Bessho
  8. Benjamin H Kwok
  9. Aimin Peng
(2020)
Kinesin Kif2C in regulation of DNA double strand break dynamics and repair
eLife 9:e53402.
https://doi.org/10.7554/eLife.53402

Share this article

https://doi.org/10.7554/eLife.53402

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