9G9L

DNA-PK + Polymerase lambda

Summary for 9G9L

• Entry DOI: 10.2210/pdb9g9l/pdb
• EMDB information: 51156
• Descriptor: DNA-dependent protein kinase catalytic subunit, X-ray repair cross-complementing protein 6, X-ray repair cross-complementing protein 5, ... (7 entities in total)
• Functional Keywords: kinase, complex, dna-binding, dna binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 7
• Total formula weight: 722106.89

Authors

Chaplin, A.K.,Amin, H.,Zahid, S.,Hardwick, S.W. (deposition date: 2024-07-25, release date: 2025-08-06, Last modification date: 2026-02-18)

Primary citation

Frit, P.,Amin, H.,Zahid, S.,Barboule, N.,Hall, C.,Matharu, G.,Hardwick, S.W.,Chauvat, J.,Britton, S.,Chirgadze, D.Y.,Ropars, V.,Charbonnier, J.B.,Calsou, P.,Chaplin, A.K.
Structural and functional insights into the interaction between Ku70/80 and Pol X family polymerases in NHEJ.
Nat Commun, 16:4208-4208, 2025

PubMed 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.

PubMed: 40328761
DOI: 10.1038/s41467-025-59133-2

Experimental method

ELECTRON MICROSCOPY (4.63 Å)