Transcription-coupled repair in yeast is independent from ubiquitylation of RNA pol II: Implications for Cockayne's syndrome

Cockayne's syndrome cells lack transcription-coupled nucleotide excision repair (TCR) and ubiquitylation of RNA polymerase II large subunit (RNA pol II LS), suggesting that ubiquitylation of RNA pol II LS may be necessary for TCR in eukaryotes. Rsp5 is the sole yeast ubiquitin-protein ligase that ubiquitylates RNA pol II LS in cells exposed to DNA-damaging agents. In yeast lacking functional Rsp5, there is no ubiquitylation of RNA pol II LS. We show here that removal, repression, or over-expression of Rsp5 has no effect on TCR, demonstrating that ubiquitylation of the RNA pol II LS is not required for TCR. We infer that the lack of ubiquitylation of RNA pol II LS in Cockayne's syndrome cells does not cause their defect in TCR.

科凯恩综合征（Cockayne's syndrome）细胞缺失转录偶联核苷酸切除修复（transcription-coupled nucleotide excision repair, TCR）以及RNA聚合酶II大亚基（RNA polymerase II large subunit, RNA pol II LS）的泛素化，这提示真核生物中RNA pol II LS的泛素化可能是TCR发挥功能的必要条件。Rsp5是酵母中唯一可在DNA损伤剂暴露的细胞内介导RNA pol II LS泛素化的泛素连接酶。在功能性Rsp5缺失的酵母菌株中，无法检测到RNA pol II LS的泛素化。本研究证实，敲除、抑制或过表达Rsp5均不会对TCR产生影响，由此表明RNA pol II LS的泛素化并非TCR发挥功能的必需条件。据此我们可以推断，科凯恩综合征细胞中RNA pol II LS泛素化的缺失，并不会导致其TCR功能缺陷。