Bacterial Proteins Involved in DNA Repair

参与 DNA 修复的细菌蛋白

• 批准号: 7194164
• 负责人: Michael M. Cox
• 金额: $ 24.63万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-03-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7194164
• 关键词: Bacteria; Bacterial Proteins; Biochemical; Bypass; Chromosomes; Collaborations; Complex; DNA; DNA Damage; DNA Repair; DNA Repair Pathway; DNA lesion; DNA polymerase V; DNA replication fork; Disease regression; Enzymes; Facility Construction Funding Category; Filament; Genetic Recombination; Goals; In Vitro; Investments; Molecular; Pathway interactions; Process; Protein Biochemistry; Proteins; Reaction; Rec A Recombinases; RecQ protein; Regulation; Resources; Restart; Role; SOS Response; Structure; System; Work; cofactor; design; helicase; multidisciplinary; novel; recombinase; reconstitution; repaired; research study

DESCRIPTION (provided by applicant): The primary function of homologous genetic recombination in bacteria is the nonmutagenic repair of arrested replication forks. Virtually every replication fork originating at oriC encounters DMA damage at some point, and must undergo recombinational DNA repair. This process represents perhaps the most complex and certainly the least understood of the major pathways for DNA repair. The work supported by GM52725 has three goals, all directed at a complete understanding of replication fork repair pathways, where the replication and recombination systems are closely integrated. The work is currently focused on the processes that regulate the function of the RecA protein. The first specific aim constitutes the major portion of the effort. The fundamental biochemistry of proteins involved in the regulation of RecA protein will be explored, focusing on the RecFOR, RecX, Dinl, RdgC, PsiB, UvrD, and RecQ proteins. RecA is regulated on multiple levels, and this effort is designed to systematically explore that regulation. An interwoven system of regulatory activities modulating almost every aspect of RecA function has been outlined in recent studies. The other two aims represent a smaller investment in effort, but allow for an integration and expansion of the information obtained in aim 1. The second aim is to reconstitute a key step in some fork repair pathways, called fork regression. This effort relies on the construction of novel DNA substrates that mimic the structure of stalled forks. The effort will draw heavily on the information provided under aim 1. The final aim is to examine the mutagenic replicative bypass of DNA lesions by DNA polymerase V in vitro. Here we are redefining the role of RecA in this repair process and potentially exploring a novel aspect of RecA regulation. These experiments will provide new information about critical parts of the pathways leading to replication fork reactivation. The ultimate goal is a complete reconstitution of the pathways with pure enzymes.

描述（由申请人提供）： 细菌中同源基因重组的主要功能是对停滞的复制叉进行非诱变性修复。事实上，每一个起源于oriC的复制叉都会在某个时候遇到DNA损伤，并且必须进行DNA重组修复。这个过程可能是最复杂的，当然也是最不了解的DNA修复的主要途径。GM52725支持的工作有三个目标，都是为了完整地理解复制叉修复途径，其中复制和重组系统紧密结合。 这项工作目前集中在调节RecA蛋白功能的过程上。第一个具体目标是这项努力的主要部分。参与RecA蛋白调节的蛋白质的基本生物化学将被探索，重点是RecFOR，RecX，Dinl，RdgC，PsiB，UvrD和RecQ蛋白。RecA在多个层面上受到监管，这项工作旨在系统地探索该监管。在最近的研究中，已经概述了一个交织的调节活动调节几乎每个方面的RecA功能的系统。其他两个目标的投入较小，但可以整合和扩展目标1中获得的信息。第二个目标是重建一些分叉修复途径中的关键步骤，称为分叉回归。这一努力依赖于模仿停滞叉结构的新型DNA底物的构建。这项工作将大量利用在目标1下提供的信息。最后的目的是研究DNA聚合酶V在体外对DNA损伤的致突变复制旁路。在这里，我们重新定义了RecA在修复过程中的作用，并可能探索RecA调控的新方面。 这些实验将提供有关导致复制叉再激活的途径的关键部分的新信息。最终目标是用纯酶完全重建这些途径。

项目成果

The single-stranded DNA-binding protein of Deinococcus radiodurans.

• DOI: 10.1186/1471-2180-4-2
• 发表时间: 2004-01-12
• 期刊: BMC microbiology
• 影响因子: 4.2
• 作者: Eggington JM;Haruta N;Wood EA;Cox MM
• 通讯作者: Cox MM

Roles of DNA polymerase V and RecA protein in SOS damage-induced mutation.

• DOI: 10.1021/cr0404951
• 发表时间: 2006-01
• 期刊: Chemical reviews
• 影响因子: 62.1
• 作者: K. Schlacher;P. Pham;M. Cox;M. Goodman

Situational repair of replication forks: roles of RecG and RecA proteins.

复制叉的情境修复：RecG 和 RecA 蛋白的作用。

• DOI: 10.1074/jbc.m312184200
• 发表时间: 2004
• 期刊: The Journal of biological chemistry
• 作者: Robu,MaraE;Inman,RossB;Cox,MichaelM
• 通讯作者: Cox,MichaelM

Allosteric effects of RuvA protein, ATP, and DNA on RuvB protein-mediated ATP hydrolysis.

RuvA 蛋白、ATP 和 DNA 对 RuvB 蛋白介导的 ATP 水解的变构作用。

• DOI: 10.1021/bi960316c
• 发表时间: 1996
• 期刊: Biochemistry.
• 作者: Marrione,PE;Cox,MM
• 通讯作者: Cox,MM

DNA polymerase V and RecA protein, a minimal mutasome.

DNA 聚合酶 V 和 RecA 蛋白（一种最小突变体）。

• DOI: 10.1016/j.molcel.2005.01.006
• 发表时间: 2005
• 期刊: Molecular cell
• 影响因子: 16
• 作者: Schlacher,Katharina;Leslie,Kris;Wyman,Claire;Woodgate,Roger;Cox,MichaelM;Goodman,MyronF
• 通讯作者: Goodman,MyronF