IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v404y2000i6774d10.1038_35004614.html
   My bibliography  Save this article

hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response

Author

Listed:
  • Jong-Soo Lee

    (Laboratory of Molecular Hematology, NHLBI, NIH)

  • Kimberly M. Collins

    (Laboratory of Molecular Hematology, NHLBI, NIH)

  • Alexandra L. Brown

    (Laboratory of Molecular Hematology, NHLBI, NIH)

  • Chang-Hun Lee

    (Laboratory of Molecular Hematology, NHLBI, NIH)

  • Jay H. Chung

    (Laboratory of Molecular Hematology, NHLBI, NIH)

Abstract

Mutations in the BRCA1 (ref. 1) tumour suppressor gene are found in almost all of the families with inherited breast and ovarian cancers and about half of the families with only breast cancer2,3. Although the biochemical function of BRCA1 is not well understood, it is important for DNA damage repair4,5,6,7 and cell-cycle checkpoint8,9,10. BRCA1 exists in nuclear foci but is hyperphosphorylated and disperses after DNA damage11,12. It is not known whether BRCA1 phosphorylation and dispersion and its function in DNA damage response are related. In yeast the DNA damage response and the replication-block checkpoint are mediated partly through the Cds1 kinase family13,14,15,16,17,18,19,20. Here we report that the human Cds1 kinase (hCds1/Chk2)21,22,23 regulates BRCA1 function after DNA damage by phosphorylating serine 988 of BRCA1. We show that hCds1 and BRCA1 interact and co-localize within discrete nuclear foci but separate after gamma irradiation. Phosphorylation of BRCA1 at serine 988 is required for the release of BRCA1 from hCds1. This phosphorylation is also important for the ability of BRCA1 to restore survival after DNA damage in the BRCA1-mutated cell line HCC1937.

Suggested Citation

  • Jong-Soo Lee & Kimberly M. Collins & Alexandra L. Brown & Chang-Hun Lee & Jay H. Chung, 2000. "hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response," Nature, Nature, vol. 404(6774), pages 201-204, March.
    • Handle: RePEc:nat:nature:v:404:y:2000:i:6774:d:10.1038_35004614
    DOI: 10.1038/35004614
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/35004614
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/35004614?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

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


    Cited by:

    1. Takuya Tsujino & Tomoaki Takai & Kunihiko Hinohara & Fu Gui & Takeshi Tsutsumi & Xiao Bai & Chenkui Miao & Chao Feng & Bin Gui & Zsofia Sztupinszki & Antoine Simoneau & Ning Xie & Ladan Fazli & Xuesen, 2023. "CRISPR screens reveal genetic determinants of PARP inhibitor sensitivity and resistance in prostate cancer," Nature Communications, Nature, vol. 14(1), pages 1-19, 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:nature:v:404:y:2000:i:6774:d:10.1038_35004614. 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.