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Cryo-EM structure of TFIIH/Rad4–Rad23–Rad33 in damaged DNA opening in nucleotide excision repair

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 initiati...

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Autores principales: van Eeuwen, Trevor, Shim, Yoonjung, Kim, Hee Jong, Zhao, Tingting, Basu, Shrabani, Garcia, Benjamin A., Kaplan, Craig D., Min, Jung-Hyun, Murakami, Kenji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184850/
https://www.ncbi.nlm.nih.gov/pubmed/34099686
http://dx.doi.org/10.1038/s41467-021-23684-x
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author van Eeuwen, Trevor
Shim, Yoonjung
Kim, Hee Jong
Zhao, Tingting
Basu, Shrabani
Garcia, Benjamin A.
Kaplan, Craig D.
Min, Jung-Hyun
Murakami, Kenji
author_facet van Eeuwen, Trevor
Shim, Yoonjung
Kim, Hee Jong
Zhao, Tingting
Basu, Shrabani
Garcia, Benjamin A.
Kaplan, Craig D.
Min, Jung-Hyun
Murakami, Kenji
author_sort van Eeuwen, Trevor
collection PubMed
description 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.
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spelling pubmed-81848502021-06-09 Cryo-EM structure of TFIIH/Rad4–Rad23–Rad33 in damaged DNA opening in nucleotide excision repair van Eeuwen, Trevor Shim, Yoonjung Kim, Hee Jong Zhao, Tingting Basu, Shrabani Garcia, Benjamin A. Kaplan, Craig D. Min, Jung-Hyun Murakami, Kenji Nat Commun Article 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. Nature Publishing Group UK 2021-06-07 /pmc/articles/PMC8184850/ /pubmed/34099686 http://dx.doi.org/10.1038/s41467-021-23684-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
van Eeuwen, Trevor
Shim, Yoonjung
Kim, Hee Jong
Zhao, Tingting
Basu, Shrabani
Garcia, Benjamin A.
Kaplan, Craig D.
Min, Jung-Hyun
Murakami, Kenji
Cryo-EM structure of TFIIH/Rad4–Rad23–Rad33 in damaged DNA opening in nucleotide excision repair
title Cryo-EM structure of TFIIH/Rad4–Rad23–Rad33 in damaged DNA opening in nucleotide excision repair
title_full Cryo-EM structure of TFIIH/Rad4–Rad23–Rad33 in damaged DNA opening in nucleotide excision repair
title_fullStr Cryo-EM structure of TFIIH/Rad4–Rad23–Rad33 in damaged DNA opening in nucleotide excision repair
title_full_unstemmed Cryo-EM structure of TFIIH/Rad4–Rad23–Rad33 in damaged DNA opening in nucleotide excision repair
title_short Cryo-EM structure of TFIIH/Rad4–Rad23–Rad33 in damaged DNA opening in nucleotide excision repair
title_sort cryo-em structure of tfiih/rad4–rad23–rad33 in damaged dna opening in nucleotide excision repair
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184850/
https://www.ncbi.nlm.nih.gov/pubmed/34099686
http://dx.doi.org/10.1038/s41467-021-23684-x
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