9CQC

The ligation complex like in the NHEJ pathway

9CQC の概要

• エントリーDOI: 10.2210/pdb9cqc/pdb
• EMDBエントリー: 45813
• 分子名称: X-ray repair cross-complementing protein 6, DNA (35-MER), 2'-deoxy-5'-O-[(R)-hydroxy{[(R)-hydroxy(phosphonooxy)phosphoryl]amino}phosphoryl]adenosine, ... (11 entities in total)
• 機能のキーワード: nhej, ligation, xlf, paxx, dna repair, ligase iv, ligase-transferase-dna complex, ligase/transferase/dna
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 855326.29

構造登録者

Li, J.,Liu, L.,Gellert, M.,Yang, W. (登録日: 2024-07-19, 公開日: 2025-04-23, 最終更新日: 2025-07-30)

主引用文献

Liu, L.,Li, J.,Cisneros-Aguirre, M.,Merkell, A.,Stark, J.M.,Gellert, M.,Yang, W.
Dynamic assemblies and coordinated reactions of non-homologous end joining.
Nature, 643:847-854, 2025

PubMed Abstract: Non-homologous end joining (NHEJ) is the main repair pathway of double-strand DNA breaks in higher eukaryotes. Here we report reconstitution of the final steps of NHEJ and structures of DNA polymerase μ and ligase IV (LIG4) engaged in gap filling and end joining. These reactions take place in a flexible ω-shaped framework composed of XRCC4 and XLF. Two broken DNA ends, each encircled by Ku70-Ku80 internally, are docked onto the ω frame, mediated by LIG4. DNA polymerase and ligase attached to each ω arm repair only one broken strand of a defined polarity; the final steps of NHEJ requires coordination and toggling of a pair of such enzymes. The facilitators XLF and PAXX additively stimulate NHEJ reactions. As DNA-end sensor and protector, LIG4 replaces DNA-PKcs for end joining and bridges the two DNA ends for polymerase to fill remaining gaps. These assemblies present new targets for NHEJ inhibition to enhance efficacy of radiotherapy and accuracy of gene editing.

PubMed: 40500445
DOI: 10.1038/s41586-025-09078-9

実験手法

ELECTRON MICROSCOPY (3.4 Å)