IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-18838-2.html
   My bibliography  Save this article

p50 mono-ubiquitination and interaction with BARD1 regulates cell cycle progression and maintains genome stability

Author

Listed:
  • Longtao Wu

    (The University of Chicago)

  • Clayton D. Crawley

    (The University of Chicago)

  • Andrea Garofalo

    (The University of Chicago)

  • Jackie W. Nichols

    (The University of Chicago)

  • Paige-Ashley Campbell

    (The University of Chicago)

  • Galina F. Khramtsova

    (The University of Chicago)

  • Olufunmilayo I. Olopade

    (The University of Chicago)

  • Ralph R. Weichselbaum

    (The University of Chicago)

  • Bakhtiar Yamini

    (The University of Chicago)

Abstract

p50, the mature product of NFKB1, is constitutively produced from its precursor, p105. Here, we identify BARD1 as a p50-interacting factor. p50 directly associates with the BARD1 BRCT domains via a C-terminal phospho-serine motif. This interaction is induced by ATR and results in mono-ubiquitination of p50 by the BARD1/BRCA1 complex. During the cell cycle, p50 is mono-ubiquitinated in S phase and loss of this post-translational modification increases S phase progression and chromosomal breakage. Genome-wide studies reveal a substantial decrease in p50 chromatin enrichment in S phase and Cycln E is identified as a factor regulated by p50 during the G1 to S transition. Functionally, interaction with BARD1 promotes p50 protein stability and consistent with this, in human cancer specimens, low nuclear BARD1 protein strongly correlates with low nuclear p50. These data indicate that p50 mono-ubiquitination by BARD1/BRCA1 during the cell cycle regulates S phase progression to maintain genome integrity.

Suggested Citation

  • Longtao Wu & Clayton D. Crawley & Andrea Garofalo & Jackie W. Nichols & Paige-Ashley Campbell & Galina F. Khramtsova & Olufunmilayo I. Olopade & Ralph R. Weichselbaum & Bakhtiar Yamini, 2020. "p50 mono-ubiquitination and interaction with BARD1 regulates cell cycle progression and maintains genome stability," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18838-2
    DOI: 10.1038/s41467-020-18838-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-18838-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-18838-2?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:11:y:2020:i:1:d:10.1038_s41467-020-18838-2. 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.