9QCS

Ku80 mediated DNA-PK dimer bound to 153 bp H2AX nucleosome

これはPDB形式変換不可エントリーです。

9QCS の概要

• エントリーDOI: 10.2210/pdb9qcs/pdb
• EMDBエントリー: 53026
• 分子名称: DNA-dependent protein kinase catalytic subunit, Histone H2B type 1-J, Histone H2AX, ... (9 entities in total)
• 機能のキーワード: dna-binding protein, nhej, ku70/80, nucleosome, dna binding protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 26
• 化学式量合計: 1657531.50

構造登録者

Hall, C.,Chaplin, A.K. (登録日: 2025-03-05, 公開日: 2026-01-14, 最終更新日: 2026-01-28)

主引用文献

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, 17:648-648, 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

実験手法

ELECTRON MICROSCOPY (4.38 Å)