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Structure of TFIIH/Rad4-Rad23-Rad33 in damaged DNA opening in Nucleotide Excision Repair

View ORCID ProfileTrevor van Eeuwen, Yoonjung Shim, Hee Jong Kim, Tingting Zhao, Shrabani Basu, Benjamin A. Garcia, View ORCID ProfileCraig Kaplan, Jung-Hyun Min, Kenji Murakami
doi: https://doi.org/10.1101/2021.01.14.426755
Trevor van Eeuwen
1Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
2Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
6Penn Center for Genome Integrity, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
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  • ORCID record for Trevor van Eeuwen
Yoonjung Shim
5Department of Chemistry and Biochemistry, Baylor University, Waco, Texas 76798, USA
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Hee Jong Kim
1Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
2Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
4Epigenetics Institute, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
6Penn Center for Genome Integrity, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
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Tingting Zhao
3Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, US
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Shrabani Basu
3Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, US
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Benjamin A. Garcia
1Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
4Epigenetics Institute, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
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Craig Kaplan
3Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, US
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Jung-Hyun Min
5Department of Chemistry and Biochemistry, Baylor University, Waco, Texas 76798, USA
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  • For correspondence: kenjim@pennmedicine.upenn.edu JungHyun_Min@baylor.edu
Kenji Murakami
1Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
6Penn Center for Genome Integrity, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
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  • For correspondence: kenjim@pennmedicine.upenn.edu JungHyun_Min@baylor.edu
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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 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 Statement

The authors have declared no competing interest.

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Posted January 15, 2021.
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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 Kaplan, Jung-Hyun Min, Kenji Murakami
bioRxiv 2021.01.14.426755; doi: https://doi.org/10.1101/2021.01.14.426755
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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 Kaplan, Jung-Hyun Min, Kenji Murakami
bioRxiv 2021.01.14.426755; doi: https://doi.org/10.1101/2021.01.14.426755

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