Cryo-EM structure of TFIIH/Rad4–Rad23–Rad33 in damaged DNA opening in nucleotide excision repair
Trevor van Eeuwen,
Yoonjung Shim,
Hee Jong Kim,
Tingting Zhao,
Shrabani Basu,
Benjamin A. Garcia,
Craig D. Kaplan,
Jung-Hyun Min () and
Kenji Murakami ()
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Trevor van Eeuwen: University of Pennsylvania
Yoonjung Shim: Baylor University
Hee Jong Kim: University of Pennsylvania
Tingting Zhao: University of Pittsburgh
Shrabani Basu: University of Pittsburgh
Benjamin A. Garcia: University of Pennsylvania
Craig D. Kaplan: University of Pittsburgh
Jung-Hyun Min: Baylor University
Kenji Murakami: University of Pennsylvania
Nature Communications, 2021, vol. 12, issue 1, 1-17
Abstract:
Abstract The versatile nucleotide excision repair (NER) pathway initiates as the XPC–RAD23B–CETN2 complex first recognizes DNA lesions from the genomic DNA and recruits the general transcription factor complex, TFIIH, for subsequent lesion verification. Here, we present a cryo-EM structure of an NER initiation complex containing Rad4–Rad23-Rad33 (yeast homologue of XPC–RAD23B–CETN2) and 7-subunit coreTFIIH assembled on a carcinogen-DNA adduct lesion at 3.9–9.2 Å resolution. A ~30-bp DNA duplex could be mapped as it straddles between Rad4 and the Ssl2 (XPB) subunit of TFIIH on the 3' and 5' side of the lesion, respectively. The simultaneous binding with Rad4 and TFIIH was permitted by an unwinding of DNA at the lesion. Translocation coupled with torque generation by Ssl2 and Rad4 would extend the DNA unwinding at the lesion and deliver the damaged strand to Rad3 (XPD) in an open form suitable for subsequent lesion scanning and verification.
Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23684-x
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DOI: 10.1038/s41467-021-23684-x
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