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-Structure paper
| タイトル | Structural and functional insights into the interaction between Ku70/80 and Pol X family polymerases in NHEJ. |
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| ジャーナル・号・ページ | Nat Commun, Vol. 16, Issue 1, Page 4208, Year 2025 |
| 掲載日 | 2025年5月6日 |
著者 | 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 Charbonnier / Patrick Calsou / Amanda K Chaplin / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:40328761 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 4.05 - 4.63 Å |
| 構造データ | EMDB-51156, PDB-9g9l: EMDB-51249, PDB-9gd7: EMDB-52550, PDB-9i04: |
| 由来 |
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キーワード | DNA BINDING PROTEIN / Kinase / complex / DNA-binding / Polymerase / enzyme / cryo-EM / NHEJ |
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