IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_ncomms13816.html
   My bibliography  Save this article

PAXX promotes KU accumulation at DNA breaks and is essential for end-joining in XLF-deficient mice

Author

Listed:
  • Xiangyu Liu

    (College of Physicians and Surgeons, Institute for Cancer Genetics, Columbia University)

  • Zhengping Shao

    (College of Physicians and Surgeons, Institute for Cancer Genetics, Columbia University)

  • Wenxia Jiang

    (College of Physicians and Surgeons, Institute for Cancer Genetics, Columbia University)

  • Brian J. Lee

    (College of Physicians and Surgeons, Institute for Cancer Genetics, Columbia University)

  • Shan Zha

    (College of Physicians and Surgeons, Institute for Cancer Genetics, Columbia University
    Hematology and Stem Cell Transplantation, College of Physicians & Surgeons, Columbia University)

Abstract

Non-homologous end-joining (NHEJ) is the most prominent DNA double strand break (DSB) repair pathway in mammalian cells. PAXX is the newest NHEJ factor, which shares structural similarity with known NHEJ factors—XRCC4 and XLF. Here we report that PAXX is dispensable for physiological NHEJ in otherwise wild-type mice. Yet Paxx−/− mice require XLF and Xlf−/− mice require PAXX for end-ligation. As such, Xlf−/−Paxx−/− mice display severe genomic instability and neuronal apoptosis, which eventually lead to embryonic lethality. Despite their structural similarities, only Xlf−/− cells, but not Paxx−/− cells require ATM/DNA-PK kinase activity for end-ligation. Mechanistically, PAXX promotes the accumulation of KU at DSBs, while XLF enhances LIG4 recruitment without affecting KU dynamics at DNA breaks in vivo. Together these findings identify the molecular functions of PAXX in KU accumulation at DNA ends and reveal distinct, yet critically complementary functions of PAXX and XLF during NHEJ.

Suggested Citation

  • Xiangyu Liu & Zhengping Shao & Wenxia Jiang & Brian J. Lee & Shan Zha, 2017. "PAXX promotes KU accumulation at DNA breaks and is essential for end-joining in XLF-deficient mice," Nature Communications, Nature, vol. 8(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms13816
    DOI: 10.1038/ncomms13816
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms13816
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms13816?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Estelle Vincendeau & Wenming Wei & Xuefei Zhang & Cyril Planchais & Wei Yu & Hélène Lenden-Hasse & Thomas Cokelaer & Juliana Pipoli da Fonseca & Hugo Mouquet & David J. Adams & Frederick W. Alt & Step, 2022. "SHLD1 is dispensable for 53BP1-dependent V(D)J recombination but critical for productive class switch recombination," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

    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:8:y:2017:i:1:d:10.1038_ncomms13816. 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.