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

• Published in: Nature communications Vol. 15; no. 1; pp. 6223 - 12
• Main Authors: Selvam, Kathiresan, Xu, Jun, Wilson, Hannah E., Oh, Juntaek, Li, Qingrong, Wang, Dong, Wyrick, John J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23-07-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 45; 45/23; 631/208/211; 631/337/1427/1430; 82/29; Amino acid sequence; Binding; Conserved sequence; Cyclobutane; Cyclobutane pyrimidine dimers; Deoxyribonucleic acid; DNA; DNA Damage; DNA Repair; DNA-directed RNA polymerase; Elongated structure; Elongation; Excision Repair; Functionals; Genomic analysis; Homology; Humanities and Social Sciences; Lesions; Mammalian cells; Mammals; multidisciplinary; Nucleotide excision repair; Nucleotide sequence; Nucleotides; Pleckstrin; Protein Binding; Protein Domains; Pyrimidine Dimers - metabolism; RNA polymerase; RNA polymerase II; RNA Polymerase II - genetics; RNA Polymerase II - metabolism; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Science; Science (multidisciplinary); Structure-function relationships; Transcription Factor TFIIH - genetics; Transcription Factor TFIIH - metabolism; Transcription, Genetic; Transcription-coupled repair; Ultraviolet Rays; Unwinding; Yeast; Yeasts
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-50539-y

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.
The elongation factor Elf1 functions in transcription coupled-nucleotide excision repair (TC-NER), but the mechanism by which yeast Elf1 promotes repair was unclear. Here, the authors show that Elf1 promotes TC-NER by binding TFIIH through a conserved sequence motif in its C-terminal domain.