Elf1 promotes Rad26's interaction with lesion-arrested Pol II for transcription-coupled repair

Authors

• Reta D. Sarsam, University of California San Diego, La Jolla, CA
• Jun Xu, University of California San Diego, La Jolla, CA
• Indrajit Lahiri, University of California San Diego, La Jolla, CA
• Wenzhi Gong, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA
• Qingrong Li, University of California San Diego, La Jolla, CA
• Juntaek Oh, University of California San Diego, La Jolla, CA
• Zhen Zhou, University of California San Diego, La Jolla, CA
• Peini Hou, University of California San Diego, La Jolla, CA
• Jenny Chong, University of California San Diego, La Jolla, CA
• Nan Hao, University of California San Diego, La Jolla, CA
• Shisheng Li, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA
• Dong Wang, University of California San Diego, La Jolla, CA
• Andres E. Leschziner, University of California San Diego, La Jolla, CA

Document Type

Article

Publication Date

1-9-2024

Publication Title

PNAS

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.

First Page

1

Last Page

10

DOI

10.1073/pnas.2314245121

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Sarsam, Reta D.; Xu, Jun; Lahiri, Indrajit; Gong, Wenzhi; Li, Qingrong; Oh, Juntaek; Zhou, Zhen; Hou, Peini; Chong, Jenny; Hao, Nan; Li, Shisheng; Wang, Dong; and Leschziner, Andres E., "Elf1 promotes Rad26's interaction with lesion-arrested Pol II for transcription-coupled repair" (2024). LSU-LCMC Cancer Center Faculty Publications. 195.
https://digitalscholar.lsuhsc.edu/llcc_facpubs/195
10.1073/pnas.2314245121