9N81

A gap-filling complex with Pol mu engaged in the NHEJ Pathway

Summary for 9N81

• Entry DOI: 10.2210/pdb9n81/pdb
• Related: 9CQ3
• EMDB information: 45807 45838 49108
• Descriptor: X-ray repair cross-complementing protein 6, DNA (37-MER), DNA-directed DNA/RNA polymerase mu, ... (13 entities in total)
• Functional Keywords: nhej, pol mu, ligation, xlf, paxx, dna repair, ligase iv, ligase-transferase-dna complex, ligase/transferase/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 20
• Total formula weight: 969297.94

Authors

Li, J.,Liu, L.,Gellert, M.,Yang, W. (deposition date: 2025-02-07, release date: 2025-04-23, Last modification date: 2025-06-25)

Primary citation

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, 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

Experimental method

ELECTRON MICROSCOPY (2.8 Å)