The Biochemistry of Genetic Recombination/RecA Protein

基因重组/RecA 蛋白的生物化学

• 批准号: 7929939
• 负责人: Michael M. Cox
• 金额: $ 29.44万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7929939
• 关键词: ATP Hydrolysis; Area; Biochemical; Biochemistry; Cells; Coupling; DNA; DNA Repair; DNA biosynthesis; DNA crosslink; DNA polymerase V; E coli RecA protein; Enzymes; Family; Filament; Genetic Recombination; Goals; Homologous Gene; Human; In Vitro; Investigation; Mediating; Molecular Models; Motor; Organism; Pathway interactions; Play; Process; Property; Protein Binding; Proteins; Reaction; Rec A Recombinases; Regulation; Research; Research Support; Role; Solutions; Structure; Structure-Activity Relationship; Tumor Suppression; Work; helicase; in vitro Model; molecular modeling; mutant; prototype; recombinase; recombinational repair; repaired; three dimensional structure; yeast protein

DESCRIPTION (provided by applicant): The RecA protein of E. coli promotes a DNA strand exchange reaction in vitro that provides a convenient molecular model for the central steps of homologous genetic recombination. This protein is the prototype for a family of recombinases found in all organisms. In humans, the primary RecA homologue (hRad51) is part of a major pathway for tumor suppression. The long-range goal of the research in this proposal is a detailed understanding of the regulation and function of RecA protein. The hypothesis that recombinational DNA repair of stalled replication forks is the primary function of RecA protein provides an intellectual framework. The project has evolved to include the RecA proteins of E. coli and D. radiodurans, as well as the Rad51 protein of yeast. There are four major areas of emphasis: (a) structure-function relationships, (b) general biochemistry of RecA family recombinases, (c) regulation of RecA, and (d) special functions of RecA protein. Structure-function efforts are focused on two initiatives. First, we are examining a number of mutant RecA proteins in which the coupling of ATP hydrolysis to one or more functions is disrupted. We also have several projects to elucidate the structure of RecA protein bound to DNA. Biochemical studies are focused on recombinase filament assembly and disassembly, DNA pairing and strand exchange, and the role of ATP hydrolysis in recombinase reactions. The work on the regulation of RecA protein includes efforts to investigate the function of the RecFOR, RecX, Dinl, RecL, RdgC, UvrD, and PsiAB proteins. Special functions of RecA under investigation include the RecA-stimulated translesion DNA synthesis reaction of DNA polymerase V, and may be extended to include a new effort to understand DNA crosslink repair.

描述（由申请人提供）：大肠杆菌的RECA蛋白在体外促进了DNA链交换反应，为同源遗传重组的中心步骤提供了方便的分子模型。该蛋白是在所有生物体中发现的重物组织酶家族的原型。在人类中，主要的RECA同源物（HRAD51）是抑制肿瘤的主要途径的一部分。该提案中研究的远程目标是对RECA蛋白的调节和功能的详细理解。 RECA蛋白的主要功能是智力框架的主要功能。该项目已演变为包括大肠杆菌和杜鹃花的RECA蛋白，以及酵母的Rad51蛋白。重点有四个主要领域：（a）结构功能关系，（b）RECA家族重组酶的一般生物化学，（c）RECA的调节和（d）RECA蛋白的特殊功能。结构功能努力集中在两个倡议上。首先，我们正在检查许多突变的RECA蛋白，其中ATP水解与一个或多个功能的偶联受到破坏。我们还有几个项目来阐明与DNA结合的RECA蛋白的结构。生化研究集中于重组酶丝组装和拆卸，DNA配对和链交换，以及ATP水解在重组酶反应中的作用。 RECA蛋白调节的工作包括研究RECFOR，RECX，DINL，RECL，RDGC，UVRD和PSIAB蛋白的功能。正在研究的RECA的特殊功能包括DNA聚合酶V的RecA刺激的Transles DNA合成反应，并且可以扩展以包括了解DNA交叉链接修复的新努力。