Structural Basis of Transcriptional Mutagenesis and Arrest of RNA Polymerase II

RNA 聚合酶 II 转录突变和抑制的结构基础

基本信息

批准号：
7512028
负责人：
Dong Wang
金额：
$ 9万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-01 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7512028
关键词：
Adopted Affect Apoptosis Base Pairing Binding Biochemistry Biological Bypass Chemical Agents Classification Complex DNA DNA Damage DNA Repair DNA biosynthesis DNA lesion DNA-Directed DNA Polymerase DNA-Directed RNA Polymerase Deoxyribonucleotides Discrimination Drug Design Elements Ensure Enzymes Gene Expression Generations Genetic Transcription Goals Interphase Cell Knowledge Life Maintenance Malignant Neoplasms Metabolism Molecular Conformation Movement Mutagenesis Nucleotides Numbers Pathway interactions Polymerase Process Proteins RNA RNA Polymerase II Radiation Recruitment Activity Regulation Research Research Personnel Resolution Ribonucleosides Ribonucleotides Roentgen Rays Signal Transduction Site Structure Substrate Interaction Suggestion Thinking Transcript Transcription Elongation Transcription-Coupled Repair Transcriptional Regulation Work X-Ray Crystallography base human disease improved insight mutant programs repaired sugar transcription factor S-II tripolyphosphate

项目摘要

DESCRIPTION (provided by applicant): The DNA templates for transcription are continuously damaged by radiation and chemical agents, as well as by products from endogenous metabolic processes. RNA polymerases encountering DNA damage may result in a number of deleterious biological consequences, such as apoptosis or mutagenesis. Transcriptional mutagenesis may be an important pathway for the generation of mutant proteins, particularly in non-dividing cells. The goal of my research is to understand how errors are avoided in transcription by RNA polymerase II (pol II). I wish to elucidate the structural basis of pol II arrest at DNA damage sites, to investigate the biological consequences of transcription arrest, and to reveal the mechanism of damage-induced transcriptional mutagenesis. My proposed research will also have implications for transcriptional regulation, DNA damage recognition, DNA repair, and rational drug design for cancer and other transcription related human diseases.

描述（由申请人提供）：用于转录的DNA模板被辐射和化学药物以及内源代谢过程的产物不断损害。遇到DNA损伤的RNA聚合酶可能导致许多有害的生物学后果，例如凋亡或诱变。转录诱变可能是产生突变蛋白的重要途径，尤其是在非分裂细胞中。我的研究的目的是了解RNA聚合酶II（POL II）如何避免转录中的错误。我希望阐明在DNA损伤部位停滞的结构基础，以研究转录停滞的生物学后果，并揭示损伤引起的转录诱变的机制。我提出的研究还将对癌症和其他相关人类疾病的转录调节，DNA损伤识别，DNA修复以及合理的药物设计具有影响。