Enhanced frequency of transcription pre-initiation complexes assembly after exposure to UV irradiation results in increased repair activity and reduced probabilities for mutagenesis

In order to survive from genotoxic challenges, cells need to adjust efficiently gene expression patterns. Recruitment of Pol II at promoters of active genes and assembly of pre-initiation complex (PIC) is the first step of gene transcription. In this study we employed time- and inhibitor- resolved experiments in order to uncover the dynamics of Pol II recruitment at promoters in UV-treated and control cells. We found that de novo recruitment of the available Pol II molecules at active promoters not only persists upon UV at all times tested (2 hours and 6 hours post UV treatment) but occurs significantly faster in the early phase of recovery (2 hours) than in unexposed human fibroblasts at the majority of active genes.

为应对基因毒性应激以维持存活，细胞需高效调控其基因表达模式。活性基因启动子区域的RNA聚合酶II（Pol II）招募与预起始复合物（pre-initiation complex, PIC）组装，是基因转录的起始步骤。本研究采用时序-抑制剂分辨率实验方案，旨在揭示紫外线（Ultraviolet, UV）处理组与对照组细胞中，启动子区域Pol II招募的动态变化规律。我们发现，在多数活性基因的启动子区域，可获取的Pol II分子的从头招募不仅在UV处理后的所有检测时间点（UV处理后2小时与6小时）均持续存在，且在恢复早期（2小时）的招募速率显著快于未受UV暴露的人成纤维细胞。