NMR Studies of Ku70 and Ku80 Domains

Ku70 和 Ku80 结构域的 NMR 研究

• 批准号: 6942385
• 负责人: Yuan Chen
• 金额: $ 36.17万
• 依托单位: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-12 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6942385
• 关键词: DNA binding protein; DNA repair; enzyme activity; intermolecular interaction; ionizing radiation; nuclear magnetic resonance spectroscopy; phosphoester ligase; protein kinase; protein structure

DESCRIPTION (provided by applicant): Protein-DNA recognition is central to many biological processes. This interaction can be classified into two major types: sequence-specific and structure-specific. DNA-repair proteins generally do not recognize specific DNA sequences but search for unusual DNA structures which require repair. In addition, the DNA repair process often requires the concerted actions of several proteins. Our understanding of the structural biology of DNA-repair process is still in its infancy. A number of major DNA repair pathways have not been characterized at the molecular level. The mechanism of structure-specific DNA recognition as well as the interactions between proteins in the repair complex is not well understood. In this proposal, we plan to characterize the major pathway for double-strand DNA breaks repair. Double-strand DNA breaks are caused by ionizing radiation, V (D) J recombination and physiological oxidation reactions, and proper repair is important to maintain genomic stability. The proteins that are central to the major pathway of double-strand-break repair process are Ku70 (69.8 kD) and Ku80 (82.7 kD). These two proteins form a tight complex, bind to broken DNA ends and recruit other proteins, including a DNA-dependent protein kinase and a DNA-ligase to form the DNA repair machinery. Previous studies suggest that the Ku proteins contain structurally and functionally independent domains. We will analyze the structures of Ku domains and study the mechanism of the interactions between these domains, and their interactions with DNA and other proteins in the DNA-repair machinery using a combination of nuclear magnetic resonance (NMR) and molecular biological approaches. These studies will provide an understanding, at the molecular level, of the assembly of the proteins at DNA double strand break sites. This information is necessary to improve our knowledge of the molecular mechanism of the Ku-mediated DNA double-strand break repair pathway. This study should also improve our understanding of the structural biology of DNA repair in general.

描述（由申请人提供）：蛋白质- dna识别是许多研究的核心

项目成果

The intrinsic affinity between E2 and the Cys domain of E1 in ubiquitin-like modifications.

• DOI: 10.1016/j.molcel.2007.05.023
• 发表时间: 2007-07
• 期刊: Molecular cell
• 影响因子: 16
• 作者: Jianghai Wang;Weidong Hu;S. Cai;Brian M. Lee;Jing Song;Yuan Chen

A high sensitivity 3D experiment for measuring Calpha-Halpha residual dipolar coupling constants.

用于测量 Calpha-Halpha 残余偶极耦合常数的高灵敏度 3D 实验。

• DOI: 10.1016/j.jmr.2003.08.008
• 发表时间: 2003
• 期刊: Journal of magnetic resonance (San Diego, Calif. : 1997)
• 作者: Hu,Weidong;Zhang,Ziming;Chen,Yuan
• 通讯作者: Chen,Yuan