IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-61864-1.html
   My bibliography  Save this article

Restriction of Ku translocation protects telomere ends

Author

Listed:
  • Stefano Mattarocci

    (UMR Stabilité Génétique Cellules Souches et Radiations)

  • Sonia Baconnais

    (Gustave Roussy)

  • Florian Roisné-Hamelin

    (UMR Stabilité Génétique Cellules Souches et Radiations)

  • Sabrina Pobiega

    (UMR Stabilité Génétique Cellules Souches et Radiations)

  • Olivier Alibert

    (Université Paris-Saclay)

  • Vincent Morin

    (Institute for Integrative Biology of the Cell (I2BC))

  • Alice Deshayes

    (UMR Stabilité Génétique Cellules Souches et Radiations)

  • Xavier Veaute

    (UMR Stabilité Génétique Cellules Souches et Radiations)

  • Virginie Ropars

    (Institute for Integrative Biology of the Cell (I2BC))

  • Maelenn Chevreuil

    (Institut Pasteur)

  • Johannes Mehringer

    (Kurt-Schwabe-Institute)

  • Didier Busso

    (UMR Stabilité Génétique Cellules Souches et Radiations)

  • Gerard Mazon

    (Gustave Roussy)

  • Paloma Fernandez Varela

    (Institute for Integrative Biology of the Cell (I2BC))

  • Éric Cam

    (Gustave Roussy)

  • Jean-Baptiste Charbonnier

    (Institute for Integrative Biology of the Cell (I2BC))

  • Philippe Cuniasse

    (Institute for Integrative Biology of the Cell (I2BC))

  • Stéphane Marcand

    (UMR Stabilité Génétique Cellules Souches et Radiations)

Abstract

Safeguarding chromosome ends against fusions via nonhomologous end joining (NHEJ) is essential for genome integrity. Paradoxically, the conserved NHEJ core factor Ku binds telomere ends. How it is prevented from promoting NHEJ remains unclear, as does the mechanism that allows Ku to coexist with telomere-protective DNA binding proteins, Rap1 in Saccharomyces cerevisiae. Here, we find that Rap1 directly inhibits Ku’s NHEJ function at telomeres. A single Rap1 molecule near a double-stand break suppresses NHEJ without displacing Ku in cells. Furthermore, Rap1 and Ku form a complex on short DNA duplexes in vitro. Cryo-EM shows Rap1 blocks Ku’s inward translocation on DNA – an essential step for NHEJ at DSBs. Nanopore sequencing of telomere fusions confirms this mechanism protects native telomere ends. These findings uncover a telomere protection mechanism where Rap1 restricts Ku’s inward translocation. This switches Ku from a repair-promoting to a protective role preventing NHEJ at telomeres.

Suggested Citation

  • Stefano Mattarocci & Sonia Baconnais & Florian Roisné-Hamelin & Sabrina Pobiega & Olivier Alibert & Vincent Morin & Alice Deshayes & Xavier Veaute & Virginie Ropars & Maelenn Chevreuil & Johannes Mehr, 2025. "Restriction of Ku translocation protects telomere ends," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61864-1
    DOI: 10.1038/s41467-025-61864-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-61864-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-61864-1?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_s41467-025-61864-1. 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.