1. Biochemistry and Chemical Biology
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Synergy between SIRT1 and SIRT6 helps recognize DNA breaks and potentiates the DNA damage response and repair in humans and mice

  1. Fanbiao Meng
  2. Minxian Qian
  3. Bin Peng
  4. Linyuan Peng
  5. Xiaohui Wang
  6. Kang Zheng
  7. Zuojun Liu
  8. Xiaolong Tang
  9. Shuju Zhang
  10. Shimin Sun
  11. Xinyue Cao
  12. Qiuxiang Pang
  13. Bosheng Zhao
  14. Wenbin Ma
  15. Zhou Songyang
  16. Bo Xu
  17. Wei-Guo Zhu
  18. Xingzhi Xu  Is a corresponding author
  19. Baohua Liu  Is a corresponding author
  1. Shenzhen University Health Science Center, China
  2. Shandong University of Technology, China
  3. Sun Yat-sen University, China
  4. Tianjin Medical University Cancer Institute and Hospital, China
Research Article
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Cite this article as: eLife 2020;9:e55828 doi: 10.7554/eLife.55828

Abstract

The DNA damage response (DDR) is a highly orchestrated process but how double-strand DNA breaks (DSBs) are initially recognized is unclear. Here, we show that polymerized SIRT6 deacetylase recognizes DSBs and potentiates the DDR in human and mouse cells. First, SIRT1 deacetylates SIRT6 at residue K33, which is important for SIRT6 polymerization and mobilization toward DSBs. Then, K33-deacetylated SIRT6 anchors to γH2AX, allowing its retention on and subsequent remodeling of local chromatin. We show that a K33R mutation that mimics hypoacetylated SIRT6 can rescue defective DNA repair as a result of SIRT1 deficiency in cultured cells. These data highlight the synergistic action between SIRTs in the spatiotemporal regulation of the DDR and DNA repair in humans and mice.

Article and author information

Author details

  1. Fanbiao Meng

    Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Shenzhen University Health Science Center, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.

  2. Minxian Qian

    Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Shenzhen University Health Science Center, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1763-2325

  3. Bin Peng

    Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Shenzhen University Health Science Center, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.

  4. Linyuan Peng

    Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Shenzhen University Health Science Center, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.

  5. Xiaohui Wang

    Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Shenzhen University Health Science Center, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.

  6. Kang Zheng

    Anti-aging & Regenerative Medicine Research Institution, School of Life Sciences, Shandong University of Technology, Zibo, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6347-4241

  7. Zuojun Liu

    Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Shenzhen University Health Science Center, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.

  8. Xiaolong Tang

    Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Shenzhen University Health Science Center, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4744-5846

  9. Shuju Zhang

    Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Shenzhen University Health Science Center, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.

  10. Shimin Sun

    Anti-aging & Regenerative Medicine Research Institution, School of Life Sciences, Shandong University of Technology, Zibo, China
    Competing interests
    The authors declare that no competing interests exist.

  11. Xinyue Cao

    Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Shenzhen University Health Science Center, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.

  12. Qiuxiang Pang

    Anti-aging & Regenerative Medicine Research Institution, School of Life Sciences, Shandong University of Technology, Zibo, China
    Competing interests
    The authors declare that no competing interests exist.

  13. Bosheng Zhao

    Anti-aging & Regenerative Medicine Research Institution, School of Life Sciences, Shandong University of Technology, Zibo, China
    Competing interests
    The authors declare that no competing interests exist.

  14. Wenbin Ma

    Key Laboratory of Gene Engineering of the Ministry of Education and State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.

  15. Zhou Songyang

    Key Laboratory of Gene Engineering of the Ministry of Education and State Key Laboratory for Biocontrol, Sun Yat-sen University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.

  16. Bo Xu

    Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
    Competing interests
    The authors declare that no competing interests exist.

  17. Wei-Guo Zhu

    Biochemistry and Molecular Biology, Shenzhen University Health Science Center, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8385-6581

  18. Xingzhi Xu

    Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Shenzhen University Health Science Center, Shenzhen, China
    For correspondence
    xingzhi.xu@szu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.

  19. Baohua Liu

    Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Shenzhen University Health Science Center, Shenzhen, China
    For correspondence
    ppliew@szu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1599-8059

Funding

National Key R&D Program of China (2017YFA0503900)

  • Wei-Guo Zhu
  • Baohua Liu

National Natural Science Foundation of China (91849208,81972602,81702909,81871114,81601215)

  • Minxian Qian
  • Zuojun Liu
  • Xiaolong Tang
  • Xingzhi Xu
  • Baohua Liu

National Natural Science Foundation of Guangdong Province (2015A030308007,2017B030301016)

  • Minxian Qian
  • Wei-Guo Zhu
  • Xingzhi Xu
  • Baohua Liu

Shenzhen Science and Technology Innovation Commission (ZDSYS20190902093401689,KQJSCX20180328093403969,JCYJ20180507182044945)

  • Baohua Liu

Tianjin Municipal Science Foundation for Youths (18JCQNJC79800)

  • Fanbiao Meng

Youth Foundation of Tianjin Medical University Cancer Institute and Hospital (B1714)

  • Fanbiao Meng

National Natural Science Foundation of China (91949124)

  • Minxian Qian

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

Reviewing Editor

  1. Matthew Simon, University of Rochester, United States

Publication history

  1. Received: February 6, 2020
  2. Accepted: June 13, 2020
  3. Accepted Manuscript published: June 15, 2020 (version 1)
  4. Version of Record published: June 29, 2020 (version 2)

Copyright

© 2020, Meng 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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