IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-59133-2.html
   My bibliography  Save this article

Structural and functional insights into the interaction between Ku70/80 and Pol X family polymerases in NHEJ

Author

Listed:
  • Philippe Frit

    (Université Toulouse III—Paul Sabatier (UT3))

  • Himani Amin

    (University of Leicester)

  • Sayma Zahid

    (University of Leicester)

  • Nadia Barboule

    (Université Toulouse III—Paul Sabatier (UT3))

  • Chloe Hall

    (University of Leicester)

  • Gurdip Matharu

    (University of Leicester)

  • Steven W. Hardwick

    (Sanger Building, University of Cambridge)

  • Jeanne Chauvat

    (Université Toulouse III—Paul Sabatier (UT3))

  • Sébastien Britton

    (Université Toulouse III—Paul Sabatier (UT3))

  • Dima Y. Chirgadze

    (Sanger Building, University of Cambridge)

  • Virginie Ropars

    (Université Paris-Saclay)

  • Jean-Baptiste Charbonnier

    (Université Paris-Saclay)

  • Patrick Calsou

    (Université Toulouse III—Paul Sabatier (UT3))

  • Amanda K. Chaplin

    (University of Leicester)

Abstract

Non-homologous end joining (NHEJ) is the main repair pathway for double-strand DNA breaks (DSBs) in mammals. DNA polymerases lambda (Pol λ) and mu (Pol μ), members of the Pol X family, play a key role in this process. However, their interaction within the NHEJ complexes is unclear. Here, we present cryo-EM structures of Pol λ in complex with the DNA-PK long-range synaptic complex, and Pol μ bound to Ku70/80-DNA. These structures identify interaction sites between Ku70/80 and Pol X BRCT domains. Using mutants at the proteins interface in functional assays including cell transfection with an original gap-filling reporter, we define the role of the BRCT domain in the recruitment and activity of the two Pol X members in NHEJ and in their contribution to cell survival following DSBs. Finally, we propose a unified model for the interaction of all Pol X members with Ku70/80.

Suggested Citation

  • Philippe Frit & Himani Amin & Sayma Zahid & Nadia Barboule & Chloe Hall & Gurdip Matharu & Steven W. Hardwick & Jeanne Chauvat & Sébastien Britton & Dima Y. Chirgadze & Virginie Ropars & Jean-Baptiste, 2025. "Structural and functional insights into the interaction between Ku70/80 and Pol X family polymerases in NHEJ," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59133-2
    DOI: 10.1038/s41467-025-59133-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-59133-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-59133-2?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:16:y:2025:i:1:d:10.1038_s41467-025-59133-2. 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.