@article{cbccd54199cc47078c2dd893587ca35c,
title = "Cryo-EM structure of TFIIH/Rad4–Rad23–Rad33 in damaged DNA opening in nucleotide excision repair",
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 {\AA} 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.",
author = "{van Eeuwen}, Trevor and Yoonjung Shim and Kim, {Hee Jong} and Tingting Zhao and Shrabani Basu and Garcia, {Benjamin A.} and Kaplan, {Craig D.} and Min, {Jung Hyun} and Kenji Murakami",
note = "Funding Information: We thank the University of Massachusetts CryoEM Core Facility, Drs. Chen Xu, KangKang Song, and Kyounghwan Lee for their constant support and assistance in data collection. We thank Dr. Sudheer Molugu and Electron Microscopy Resource Laboratory at the University of Pennsylvania for use of equipment and assistance with cryo-EM sample screening. Some of this work was performed at the National Center for CryoEM Access and Training (NCCAT) and the Simons Electron Microscopy Center located at the New York Structural Biology Center, supported by the NIH Common Fund Transformative High-Resolution Cryo-Electron Microscopy program (U24 GM129539), and by grants from the Simons Foundation (SF349247) and NY State. We thank Drs. Yi-Wei Chang and Shrawan Mageswaran for assistance with data analysis by cryo-electron tomography. We would like to thank Dr. Geoffrey Dann for his assistance in purifying AAF substrates. This research was supported by NIH R01-GM123233 to K.M., NIH R01GM120450 to C.D.K., NSF grant MCB-1412692, and NIH grant R21-ES028384 to J.-H.M., NIH grant P01CA196539 to B.A.G.; NIH training grants T32-GM008275 to T.V.E. and T32-GM071339 to H.J.K. Computational resources were supported by NIH Project Grant S10OD023592. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1038/s41467-021-23684-x",
language = "English",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
number = "1",
}