IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-09641-9.html
   My bibliography  Save this article

Pellino1 regulates reversible ATM activation via NBS1 ubiquitination at DNA double-strand breaks

Author

Listed:
  • Geun-Hyoung Ha

    (Sungkyunkwan University School of Medicine)

  • Jae-Hoon Ji

    (Ajou University School of Medicine)

  • Sunyoung Chae

    (Ajou University School of Medicine)

  • Jihyun Park

    (Sungkyunkwan University)

  • Suhyeon Kim

    (Sungkyunkwan University School of Medicine)

  • Jin-Kwan Lee

    (Sungkyunkwan University)

  • Yonghyeon Kim

    (Ajou University School of Medicine)

  • Sunwoo Min

    (Ajou University School of Medicine
    Ajou University School of Medicine)

  • Jeong-Min Park

    (Dong-A University)

  • Tae-Hong Kang

    (Dong-A University)

  • Ho Lee

    (Graduate School of Cancer Science and Policy, Research Institute, National Cancer Center)

  • Hyeseong Cho

    (Ajou University School of Medicine
    Ajou University School of Medicine)

  • Chang-Woo Lee

    (Sungkyunkwan University School of Medicine
    Sungkyunkwan University)

Abstract

DNA double-strand break (DSB) signaling and repair are critical for genome integrity. They rely on highly coordinated processes including posttranslational modifications of proteins. Here we show that Pellino1 (Peli1) is a DSB-responsive ubiquitin ligase required for the accumulation of DNA damage response proteins and efficient homologous recombination (HR) repair. Peli1 is activated by ATM-mediated phosphorylation. It is recruited to DSB sites in ATM- and γH2AX-dependent manners. Interaction of Peli1 with phosphorylated histone H2AX enables it to bind to and mediate the formation of K63-linked ubiquitination of NBS1, which subsequently results in feedback activation of ATM and promotes HR repair. Collectively, these results provide a DSB-responsive factor underlying the connection between ATM kinase and DSB-induced ubiquitination.

Suggested Citation

  • Geun-Hyoung Ha & Jae-Hoon Ji & Sunyoung Chae & Jihyun Park & Suhyeon Kim & Jin-Kwan Lee & Yonghyeon Kim & Sunwoo Min & Jeong-Min Park & Tae-Hong Kang & Ho Lee & Hyeseong Cho & Chang-Woo Lee, 2019. "Pellino1 regulates reversible ATM activation via NBS1 ubiquitination at DNA double-strand breaks," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09641-9
    DOI: 10.1038/s41467-019-09641-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-09641-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-09641-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09641-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.