IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-52250-4.html
   My bibliography  Save this article

USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication

Author

Listed:
  • Hannah L. Mackay

    (University of Birmingham)

  • Helen R. Stone

    (University of Birmingham
    University of Birmingham)

  • George E. Ronson

    (University of Birmingham)

  • Katherine Ellis

    (University of Birmingham
    University of Sheffield)

  • Alexander Lanz

    (University of Birmingham)

  • Yara Aghabi

    (University of Birmingham)

  • Alexandra K. Walker

    (University of Birmingham)

  • Katarzyna Starowicz

    (University of Birmingham
    Lyndon House)

  • Alexander J. Garvin

    (University of Birmingham
    University of Leeds)

  • Patrick Van Eijk

    (Hinxton
    Heath Park)

  • Stefan A. Koestler

    (University of Birmingham)

  • Elizabeth J. Anthony

    (University of Birmingham)

  • Ann Liza Piberger

    (University of Birmingham)

  • Anoop S. Chauhan

    (University of Birmingham)

  • Poppy Conway-Thomas

    (University of Birmingham)

  • Alina Vaitsiankova

    (Falmer
    Columbia University Irving Medical Center)

  • Sobana Vijayendran

    (University of Birmingham
    Mindelsohn Way)

  • James F. Beesley

    (University of Birmingham)

  • Eva Petermann

    (University of Birmingham)

  • Eric J. Brown

    (University of Pennsylvania)

  • Ruth M. Densham

    (University of Birmingham)

  • Simon H. Reed

    (Hinxton
    Heath Park)

  • Felix Dobbs

    (Hinxton
    Heath Park)

  • Marco Saponaro

    (University of Birmingham)

  • Joanna R. Morris

    (University of Birmingham)

Abstract

Mammalian DNA replication relies on various DNA helicase and nuclease activities to ensure accurate genetic duplication, but how different helicase and nuclease activities are properly directed remains unclear. Here, we identify the ubiquitin-specific protease, USP50, as a chromatin-associated protein required to promote ongoing replication, fork restart, telomere maintenance, cellular survival following hydroxyurea or pyridostatin treatment, and suppression of DNA breaks near GC-rich sequences. We find that USP50 supports proper WRN-FEN1 localisation at or near stalled replication forks. Nascent DNA in cells lacking USP50 shows increased association of the DNA2 nuclease and RECQL4 and RECQL5 helicases and replication defects in cells lacking USP50, or FEN1 are driven by these proteins. Consequently, suppression of DNA2 or RECQL4/5 improves USP50-depleted cell resistance to agents inducing replicative stress and restores telomere stability. These data define an unexpected regulatory protein that promotes the balance of helicase and nuclease use at ongoing and stalled replication forks.

Suggested Citation

  • Hannah L. Mackay & Helen R. Stone & George E. Ronson & Katherine Ellis & Alexander Lanz & Yara Aghabi & Alexandra K. Walker & Katarzyna Starowicz & Alexander J. Garvin & Patrick Van Eijk & Stefan A. K, 2024. "USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52250-4
    DOI: 10.1038/s41467-024-52250-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-52250-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-52250-4?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:15:y:2024:i:1:d:10.1038_s41467-024-52250-4. 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.