9Q9F

DNA-PK bound to a 153 bp H2AX nucleosome model 1

This is a non-PDB format compatible entry.

Summary for 9Q9F

• Entry DOI: 10.2210/pdb9q9f/pdb
• EMDB information: 52958
• Descriptor: X-ray repair cross-complementing protein 6, X-ray repair cross-complementing protein 5, DNA, ... (9 entities in total)
• Functional Keywords: dna-binding protein, nhej, ku70/80, nucleosome, dna binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 13
• Total formula weight: 828765.75

Authors

Hall, C.,Chaplin, A.K. (deposition date: 2025-02-26, release date: 2026-01-14)

Primary citation

Hall, C.,Frit, P.,Kefala-Stavridi, A.,Pelletier, A.,Hardwick, S.W.,Amin, H.,Bilyard, M.K.,Maia De Oliviera, T.,Tariq, A.,Zahid, S.,Chirgadze, D.Y.,Balasubramanian, S.,Meek, K.,Ropars, V.,Charbonnier, J.B.,Modesti, M.,Calsou, P.,Britton, S.,Blundell, T.L.,Schalch, T.,Chaplin, A.K.
Cryo-EM structures of NHEJ assemblies with nucleosomes.
Nat Commun, 2025

PubMed Abstract: DNA double-strand breaks (DSBs) are highly deleterious lesions that can trigger cell death or carcinogenesis if unrepaired or misrepaired. In mammals, most DSBs are repaired by non-homologous end joining (NHEJ), which begins when Ku70/80 binds DNA ends and recruits DNA-PKcs to form the DNA-PK holoenzyme. Although recent cryo-EM studies have resolved several NHEJ assemblies, how these factors access DSBs within nucleosomes remains unclear. Here, we present cryo-EM structures of human Ku70/80 and DNA-PK bound to nucleosomes. Ku70/80 binds the DNA end and bends it away from the nucleosome core, while the Ku70 C-terminal SAP domain makes an additional, specific DNA contact. Our DNA-PK-nucleosome structure further reveals the opening of the Ku80 vWA domain, and we show that non-hydrolysable ATP promotes synapsis by stabilising the Ku80-mediated DNA-PK dimer. These structures reveal a model for DSB recognition on nucleosomal DNA and provide insights relevant to targeting NHEJ in cancer therapy.

PubMed: 41444611
DOI: 10.1038/s41467-025-67376-2

Experimental method

ELECTRON MICROSCOPY (4.54 Å)