Nucleotide Excision Repair in Escherichia Coli

大肠杆菌中的核苷酸切除修复

• 批准号: 8802091
• 负责人: Anthony Yeung
• 金额: $ 26.82万
• 依托单位: Institute For Cancer Research
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8802091&HistoricalAwards=false
• 关键词: Nucleotide; Excision; Repair; Escherichia; Coli

Many foreign agents form covalent adducts with DNA. These lesions are removed by nucleotide excision repair systems such as the UvrABC endonuclease system of E. coli. The mechanism and efficiency of repair may depend on the DNA structure at the site of the lesion. Using homogeneous substrates specifically modified with a psoralen monoadduct or crosslink, DNA sequences and helix conformation will be related to the in vitro efficiency of DNA repair. Protein DNA complexes and intermediate products will be analyzed in order to formulate biochemical mechanisms of repair. It is proposed to test whether the rate of repair of a crosslink depends on the DNA conformation; whether fast repair is due to rapid incision by UvrABC endonuclease and whether slow repair may form a high affinity UvrAB-lesion nucleoprotein complex which promotes subsequent slower steps such as recombinational repair. Nucleotide Excision DNA repair is a natural cellular defense mechanism by which a cell, using multienzyme complexes rids itself of a variety of lesions in its DNA. A feature in common among these DNA lesions may be a distortion of the local DNA conformation which becomes attractive to the nucleotide excision repair enzymes, allowing this enzyme system to exhibit a broad range of substrate specificity. In more complex DNA lesions repair may also require the participation of DNA recombinant enzymes. Dr. Yeung will study the repair of psoralen-DNA monoadducts and crosslinks in purified system using a number of repair enzymes and defined DNA substrates in order to better understand the mechanism of this important cellular process.

许多外源因子与DNA形成共价加合物。 这些 通过核苷酸切除修复系统去除损伤， 与E.杆菌 机制 修复的效率可能取决于DNA结构， 病变部位。 使用均匀的基质， 修饰有一种单加合物或交联物的DNA 序列和螺旋构象将与 DNA修复的体外效率。 蛋白质DNA复合物和 将分析中间产物以配制 修复的生化机制 建议测试 交联的修复速率是否取决于DNA 构造;快速修复是否是由于快速切口 UvrABC核酸内切酶和缓慢修复是否可能形成高表达 亲和性UvrAB-损伤核蛋白复合物， 随后的较慢步骤，如重组修复。 DNA修复是一种天然的细胞修复过程。 细胞利用多酶复合物的防御机制 摆脱了DNA中的各种损伤。 中的特征 在这些DNA损伤中常见的可能是局部DNA的扭曲， 对核苷酸具有吸引力的DNA构象 切除修复酶，允许这种酶系统表现出 广泛的底物特异性。 在更复杂的DNA 损伤修复也可能需要DNA的参与 重组酶 杨医生将研究 纯化体系中的磷脂-DNA单加合物和交联 使用许多修复酶和确定的DNA底物， 为了更好地了解这一重要的机制， 细胞过程