Elf1 promotes transcription-coupled repair in yeast by using its C-terminal domain to bind TFIIH.

Autor: Selvam K; School of Molecular Biosciences, Washington State University, Pullman, WA, USA., Xu J; Division of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.; Genetics and Metabolism Department, The Children's Hospital, School of Medicine, Zhejiang University, National Clinical Research Center for Child Health, Hangzhou, China., Wilson HE; School of Molecular Biosciences, Washington State University, Pullman, WA, USA., Oh J; Division of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.; Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea., Li Q; Division of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA., Wang D; Division of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA. dongwang@ucsd.edu.; Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, CA, USA. dongwang@ucsd.edu.; Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA. dongwang@ucsd.edu., Wyrick JJ; School of Molecular Biosciences, Washington State University, Pullman, WA, USA. jwyrick@wsu.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jul 23; Vol. 15 (1), pp. 6223. Date of Electronic Publication: 2024 Jul 23.
DOI: 10.1038/s41467-024-50539-y
Abstrakt: Transcription coupled-nucleotide excision repair (TC-NER) removes DNA lesions that block RNA polymerase II (Pol II) transcription. A key step in TC-NER is the recruitment of the TFIIH complex, which initiates DNA unwinding and damage verification; however, the mechanism by which TFIIH is recruited during TC-NER, particularly in yeast, remains unclear. Here, we show that the C-terminal domain (CTD) of elongation factor-1 (Elf1) plays a critical role in TC-NER in yeast by binding TFIIH. Analysis of genome-wide repair of UV-induced cyclobutane pyrimidine dimers (CPDs) using CPD-seq indicates that the Elf1 CTD in yeast is required for efficient TC-NER. We show that the Elf1 CTD binds to the pleckstrin homology (PH) domain of the p62 subunit of TFIIH in vitro, and identify a putative TFIIH-interaction region (TIR) in the Elf1 CTD that is important for PH binding and TC-NER. The Elf1 TIR shows functional, structural, and sequence similarities to a conserved TIR in the mammalian UV sensitivity syndrome A (UVSSA) protein, which recruits TFIIH during TC-NER in mammalian cells. These findings suggest that the Elf1 CTD acts as a functional counterpart to mammalian UVSSA in TC-NER by recruiting TFIIH in response to Pol II stalling at DNA lesions.
(© 2024. The Author(s).)
Databáze: MEDLINE
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