Elf1 promotes TC-NER in yeast by using its C-terminal domain to bind TFIIH

Transcription coupled-nucleotide excision repair (TC-NER) repairs DNA lesions that stall RNA polymerase II (Pol II) transcription. Here, we show that the C-terminal domain (CTD) of elongation factor-1 (Elf1) plays a critical role in TC-NER in yeast. Analysis of genome-wide repair of UV-induced cyclobutane pyrimidine dimers (CPDs) using CPD-seq indicates that the Elf1 CTD is required for efficient Rad26-dependent and Rad26-independent TC-NER across the yeast genome. The Elf1-CTD is also important for TC-NER in rad16∆ cells deficient in GG-NER. Finally, we show that a mutant in the Elf1-CTD (elf1-Y99A) that disrupts binding to a subunit of TFIIH affects Rad26-independent repair in a rad26∆ mutant background.转录偶联核苷酸切除修复（Transcription coupled-nucleotide excision repair, TC-NER）负责修复阻断RNA聚合酶II（RNA polymerase II, Pol II）转录的DNA损伤。本研究表明，酵母中延伸因子-1（elongation factor-1, Elf1）的C端结构域（C-terminal domain, CTD）在TC-NER过程中发挥关键作用。通过CPD测序（CPD-seq）技术对紫外线诱导的环丁烷嘧啶二聚体（UV-induced cyclobutane pyrimidine dimers, CPDs）开展全基因组修复分析，结果显示，Elf1的CTD是酵母基因组范围内高效完成依赖Rad26与不依赖Rad26的TC-NER所必需的。此外，Elf1-CTD对于全局基因组核苷酸切除修复（global genome nucleotide excision repair, GG-NER）缺陷型rad16∆细胞中的TC-NER同样至关重要。最后，本研究证实，Elf1-CTD中破坏其与转录因子IIH（TFIIH）某亚基结合的突变体elf1-Y99A，会在rad26∆突变背景下影响不依赖Rad26的修复过程。