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
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