Role of RNA polymerase in DNA stability and repair

RNA 聚合酶在 DNA 稳定性和修复中的作用

基本信息

批准号：
8914643
负责人：
EVGENY A NUDLER
金额：
$ 41.53万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2018-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8914643
关键词：
ATP Hydrolysis Address Amino Acids Bacteria Bacterial RNA Base Excision Repairs Binding Biochemical Biological Assay Cells ChIP-seq Complex Conflict (Psychology)DNA DNA Damage DNA Maintenance DNA Repair DNA lesion DNA-Directed RNA Polymerase Data Escherichia coli Excision Fluorescence Microscopy Fluorescence Resonance Energy Transfer Genetic Genetic Transcription Genome Genome Stability Genotoxic Stress Head Health Human In Vitro Investigation Lesion Maps Mass Spectrum Analysis Mediating Modification Molecular Molecular Conformation Monitor Motor Movement Mutagenesis Nucleotide Excision Repair Organism Pathway interactions Phase Physiological Plasmids Play Process Proteins Proteomics Recovery Research Research Design Resistance Resolution Role SOS Response Series Site Solid Stress Structural Models System Testing Transcript Transcription Elongation Transcription-Coupled Repair X-Ray Crystallography base design enzyme activity genome-wide helicase in vivo protein crosslink reconstitution repair enzyme repaired research study sensor single molecule stoichiometry structural genomics translocase

项目摘要

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.

描述（由申请人提供）：该提案重点阐明细菌 RNA 聚合酶作为全基因组 DNA 损伤监视工具的生化、生理和结构方面的作用，并解决其与复制体的碰撞。 RNA 聚合酶的逆行运动（称为回溯）已被证明在这两个过程中都发挥着至关重要的作用。我们已经确定了几种重要的 RNA 聚合酶相关因子，特别是 UvrD 解旋酶和 GreA/B 裂解因子，它们刺激或拮抗回溯，并对细胞对基因毒性物质的抵抗力产生巨大影响。在这里，我们提出了一套全面的生物化学、生物物理、遗传、基因组学和结构蛋白质组学实验，旨在深入研究从分子到细胞的转录相关现象的各个方面。