Role of RNA polymerase in DNA stability and repair

描述(由申请人提供)：本提案侧重于阐明细菌RNA聚合酶作为全基因组DNA损伤监测工具的生化、生理和结构方面的作用，以及解决其与复制体的冲突。RNA聚合酶的逆行运动，即所谓的回溯，已被证明在这两个过程中都发挥了关键作用。我们已经确定了几个重要的RNA聚合酶相关因子，特别是UvrD解旋酶和GreA/B裂解因子，它们可以刺激或拮抗回溯，并对细胞对遗传毒性物质的抗性产生巨大影响。在这里，我们提出了一套全面的生化、生物物理、遗传学、基因组学和结构蛋白质组学实验，旨在深入研究这种转录相关现象的各个方面，从分子到细胞。

DESCRIPTION (provided by applicant): This proposal focuses on elucidation of biochemical, physiological, and structural aspects of bacterial RNA polymerase role as a genome-wide DNA damage surveillance vehicle and resolution of its collisions with replisome. Retrograde movement of RNA polymerase, known is backtracking, has been shown to play crucial role in both processes. We have identified several important RNA polymerase-associated factors, particularly UvrD helicase and GreA/B cleavage factors, that stimulate or antagonize backtracking, and have tremendous impact on cell resistance to genotoxic substances. Here we propose a comprehensive set of biochemical, biophysical, genetic, genomics, and structural proteomics experiments aiming at in-depth investigation of all aspects, from molecular to cellular, of this spectrum of transcription-related phenomena.