Sarsam, R.D. orcid.org/0000-0003-3816-2470, Xu, J., Lahiri, I. orcid.org/0000-0002-5633-7978 et al. (10 more authors) (2024) Elf1 promotes Rad26’s interaction with lesion-arrested Pol II for transcription-coupled repair. Proceedings of the National Academy of Sciences, 121 (3). e2314245121. ISSN 0027-8424
Abstract
Transcription-coupled nucleotide excision repair (TC-NER) is a highly conserved DNA repair pathway that removes bulky lesions in the transcribed genome. Cockayne syndrome B protein (CSB), or its yeast ortholog Rad26, has been known for decades to play important roles in the lesion-recognition steps of TC-NER. Another conserved protein ELOF1, or its yeast ortholog Elf1, was recently identified as a core transcription-coupled repair factor. How Rad26 distinguishes between RNA polymerase II (Pol II) stalled at a DNA lesion or other obstacles and what role Elf1 plays in this process remains unknown. Here, we present cryo-EM structures of Pol II-Rad26 complexes stalled at different obstacles that show that Rad26 uses a common mechanism to recognize a stalled Pol II, with additional interactions when Pol II is arrested at a lesion. A cryo-EM structure of lesion-arrested Pol II-Rad26 bound to Elf1 revealed that Elf1 induces further interactions between Rad26 and a lesion-arrested Pol II. Biochemical and genetic data support the importance of the interplay between Elf1 and Rad26 in TC-NER initiation. Together, our results provide important mechanistic insights into how two conserved transcription-coupled repair factors, Rad26/CSB and Elf1/ELOF1, work together at the initial lesion recognition steps of transcription-coupled repair.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY - https://creativecommons.org/licenses/by/4.0/). |
Keywords: | Cockayne syndrome B; Elf1; RNA polymerase II; cryo-EM; transcription-coupled repair; Humans; Cognition; DNA Damage; Excision Repair; Heart Arrest; RNA Polymerase II; Saccharomyces cerevisiae |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 04 Jul 2024 07:39 |
Last Modified: | 04 Jul 2024 07:39 |
Status: | Published |
Publisher: | Proceedings of the National Academy of Sciences |
Refereed: | Yes |
Identification Number: | 10.1073/pnas.2314245121 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:214407 |