IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v431y2004i7011d10.1038_nature02964.html
   My bibliography  Save this article

DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1

Author

Listed:
  • Grzegorz Ira

    (Brandeis University)

  • Achille Pellicioli

    (F.I.R.C. Institute of Molecular Oncology Foundation
    Universitá degli Studi di Milano)

  • Alitukiriza Balijja

    (F.I.R.C. Institute of Molecular Oncology Foundation
    Universitá degli Studi di Milano)

  • Xuan Wang

    (Brandeis University
    Rockefeller University)

  • Simona Fiorani

    (F.I.R.C. Institute of Molecular Oncology Foundation
    Universitá degli Studi di Milano)

  • Walter Carotenuto

    (F.I.R.C. Institute of Molecular Oncology Foundation
    Universitá degli Studi di Milano)

  • Giordano Liberi

    (F.I.R.C. Institute of Molecular Oncology Foundation
    Universitá degli Studi di Milano)

  • Debra Bressan

    (Brandeis University)

  • Lihong Wan

    (SUNY Stony Brook)

  • Nancy M. Hollingsworth

    (SUNY Stony Brook)

  • James E. Haber

    (Brandeis University)

  • Marco Foiani

    (F.I.R.C. Institute of Molecular Oncology Foundation
    Universitá degli Studi di Milano)

Abstract

A single double-strand break (DSB) induced by HO endonuclease triggers both repair by homologous recombination and activation of the Mec1-dependent DNA damage checkpoint in budding yeast1,2,3,4,5,6. Here we report that DNA damage checkpoint activation by a DSB requires the cyclin-dependent kinase CDK1 (Cdc28) in budding yeast. CDK1 is also required for DSB-induced homologous recombination at any cell cycle stage. Inhibition of homologous recombination by using an analogue-sensitive CDK1 protein7,8 results in a compensatory increase in non-homologous end joining. CDK1 is required for efficient 5′ to 3′ resection of DSB ends and for the recruitment of both the single-stranded DNA-binding complex, RPA, and the Rad51 recombination protein. In contrast, Mre11 protein, part of the MRX complex, accumulates at unresected DSB ends. CDK1 is not required when the DNA damage checkpoint is initiated by lesions that are processed by nucleotide excision repair. Maintenance of the DSB-induced checkpoint requires continuing CDK1 activity that ensures continuing end resection. CDK1 is also important for a later step in homologous recombination, after strand invasion and before the initiation of new DNA synthesis.

Suggested Citation

  • Grzegorz Ira & Achille Pellicioli & Alitukiriza Balijja & Xuan Wang & Simona Fiorani & Walter Carotenuto & Giordano Liberi & Debra Bressan & Lihong Wan & Nancy M. Hollingsworth & James E. Haber & Marc, 2004. "DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1," Nature, Nature, vol. 431(7011), pages 1011-1017, October.
    • Handle: RePEc:nat:nature:v:431:y:2004:i:7011:d:10.1038_nature02964
    DOI: 10.1038/nature02964
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature02964
    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/nature02964?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. Adrián Campos & Facundo Ramos & Lydia Iglesias & Celia Delgado & Eva Merino & Antonio Esperilla-Muñoz & Jaime Correa-Bordes & Andrés Clemente-Blanco, 2023. "Cdc14 phosphatase counteracts Cdk-dependent Dna2 phosphorylation to inhibit resection during recombinational DNA repair," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Daipayan Banerjee & Kurt Langberg & Salar Abbas & Eric Odermatt & Praveen Yerramothu & Martin Volaric & Matthew A. Reidenbach & Kathy J. Krentz & C. Dustin Rubinstein & David L. Brautigan & Tarek Abba, 2021. "A non-canonical, interferon-independent signaling activity of cGAMP triggers DNA damage response signaling," Nature Communications, Nature, vol. 12(1), pages 1-24, 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:431:y:2004:i:7011:d:10.1038_nature02964. 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.