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

• 成果类型: Article
• 署名作者: Sarsam, Reta D.; Xu, Jun; Lahiri, Indrajit; Gong, Wenzhi; Li, Qingrong; Oh, Juntaek; Zhou, Zhen; Hou, Peini; Chong, Jenny; Hao, Nan; Lic, Shisheng; Wang, Dong; Leschziner, Andres E.
• 署名单位: Charles River Laboratories; Zhejiang University; University of Sheffield; Kyung Hee University; University of California System; University of California San Diego; University of California System; University of California San Diego; Louisiana State University School of Veterinary Medicine; Louisiana State University System; Louisiana State University; University of California System; University of California San Diego; University of California System; University of California San Diego
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10962
• DOI: 10.1073/pnas.2314245121
• 发表日期: 2024-01-16
• 关键词: rna-polymerase-ii; cockayne-syndrome; elongation-factor; dna-damage; cryo-em; structural basis; protein; Visualization; refinement; SYSTEM

摘要

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 dec-ades 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.