RT Journal Article
SR Electronic
T1 Structure of TFIIH/Rad4-Rad23-Rad33 in damaged DNA opening in Nucleotide Excision Repair
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.14.426755
DO 10.1101/2021.01.14.426755
A1 Trevor van Eeuwen
A1 Yoonjung Shim
A1 Hee Jong Kim
A1 Tingting Zhao
A1 Shrabani Basu
A1 Benjamin A. Garcia
A1 Craig Kaplan
A1 Jung-Hyun Min
A1 Kenji Murakami
YR 2021
UL http://biorxiv.org/content/early/2021/01/15/2021.01.14.426755.abstract
AB 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 core TFIIH 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 would extend the DNA opening at the lesion and deliver the damaged strand to Rad3 (XPD) in an unwound form suitable for subsequent lesion scanning and verification.Competing Interest StatementThe authors have declared no competing interest.