Lesion recognition by XPC, TFIIH and XPA in DNA excision repair
Jinseok Kim,
Chia-Lung Li,
Xuemin Chen,
Yanxiang Cui,
Filip M. Golebiowski,
Huaibin Wang,
Fumio Hanaoka,
Kaoru Sugasawa () and
Wei Yang ()
Additional contact information
Jinseok Kim: Laboratory of Molecular Biology, NIDDK, National Institutes of Health
Chia-Lung Li: Laboratory of Molecular Biology, NIDDK, National Institutes of Health
Xuemin Chen: Laboratory of Molecular Biology, NIDDK, National Institutes of Health
Yanxiang Cui: Laboratory of Cell and Molecular Biology, NIDDK, National Institutes of Health
Filip M. Golebiowski: Laboratory of Molecular Biology, NIDDK, National Institutes of Health
Huaibin Wang: Laboratory of Cell and Molecular Biology, NIDDK, National Institutes of Health
Fumio Hanaoka: National Institute of Genetics, Research Organization of Information and Systems
Kaoru Sugasawa: Kobe University
Wei Yang: Laboratory of Molecular Biology, NIDDK, National Institutes of Health
Nature, 2023, vol. 617, issue 7959, 170-175
Abstract:
Abstract Nucleotide excision repair removes DNA lesions caused by ultraviolet light, cisplatin-like compounds and bulky adducts1. After initial recognition by XPC in global genome repair or a stalled RNA polymerase in transcription-coupled repair, damaged DNA is transferred to the seven-subunit TFIIH core complex (Core7) for verification and dual incisions by the XPF and XPG nucleases2. Structures capturing lesion recognition by the yeast XPC homologue Rad4 and TFIIH in transcription initiation or DNA repair have been separately reported3–7. How two different lesion recognition pathways converge and how the XPB and XPD helicases of Core7 move the DNA lesion for verification are unclear. Here we report on structures revealing DNA lesion recognition by human XPC and DNA lesion hand-off from XPC to Core7 and XPA. XPA, which binds between XPB and XPD, kinks the DNA duplex and shifts XPC and the DNA lesion by nearly a helical turn relative to Core7. The DNA lesion is thus positioned outside of Core7, as would occur with RNA polymerase. XPB and XPD, which track the lesion-containing strand but translocate DNA in opposite directions, push and pull the lesion-containing strand into XPD for verification.
Date: 2023
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DOI: 10.1038/s41586-023-05959-z
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