9PD5

NER dual incision complex - NoF

Summary for 9PD5

• Entry DOI: 10.2210/pdb9pd5/pdb
• EMDB information: 71526
• Descriptor: TFIIH basal transcription factor complex helicase XPB subunit, DNA, DNA excision repair protein ERCC-5, ... (13 entities in total)
• Functional Keywords: ner, xpa, xpg, xpf, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 11
• Total formula weight: 602056.47

Authors

Li, C.L.,Kim, J.,Yang, W. (deposition date: 2025-06-30, release date: 2026-02-18, Last modification date: 2026-04-01)

Primary citation

Li, E.C.L.,Kim, J.,Brussee, S.J.,Sugasawa, K.,Luijsterburg, M.S.,Yang, W.
Pre-incision structures reveal principles of DNA nucleotide excision repair.
Nature, 2026

PubMed Abstract: Nucleotide excision repair (NER) removes bulky adducts from genomic DNA and prevents the ultraviolet light-sensitivity disease xeroderma pigmentosum, cancer and premature ageing. After initial lesion recognition by XPC in global genome repair or by stalled RNA polymerases in transcription-coupled repair, a lesion and surrounding DNA duplex are unwound by TFIIH, which includes the ATPases XPB and XPD, and additional NER factors XPA, XPF, XPG and RPA, to form a DNA bubble comprising around 27 nucleotides. The double strand-single strand (ds-ss) junction-specific endonucleases XPF and XPG cleave DNA on the 5' and 3' sides of the lesion, respectively. Here we report the functional steps and atomic structures of the ATPase-driven and lesion-dependent DNA bubble formation and arrangement of the complete NER factors for dual incision. The unwinding of nearly 30 base pairs of DNA depends mainly on the double strand DNA translocase XPB and the duplex dividers XPA and XPF. XPD binds the lesion strand with XPF at the 5' ds-ss junction. XPF cuts the lesion strand only after XPG binds the 3' ds-ss junction. The ERCC1 subunit of XPF facilitates DNA strand separation and recruitment of RPA to the non-lesion strand. These findings provide insights on the causes of human diseases and potential targets for enhancing chemotherapeutic efficacy.

PubMed: 41673165
DOI: 10.1038/s41586-026-10122-5

Experimental method

ELECTRON MICROSCOPY (5.7 Å)