STRUCTURE AND FUNCTION OF HOMOLOGOUS RECOMBINATION ENZYMES

同源重组酶的结构和功能

基本信息

项目摘要

Double-strand break repair (DSBR) by homologous recombination repairs double strand breaks produced by ionizing radiation and this DNA repair process is conserved from bacteriophage to humans. In all organisms, homologous DSBR requires the DNA strand exchange activity of an ortholog of the E. coli RecA protein. The RecA family is the most highly sequence-conserved family of DNA repair proteins, which exhibits strong conservation of global structure and function in promoting homologous recombination and DSBR transactions. Nevertheless, RecAs for which biochemical data are available exhibit surprising diversity in DNA binding properties, catalysis, and allosteric mechanisms, while others appear to be specialized recombination mediators. Does this diversity/specialization reflect different evolutionary paths towards RecA function? Also, to what extent does RecA biochemical diversity/specialization reflect the environmental demands placed on the DNA recombination and repair systems of a host organism? The work proposed in this Project intends to address these questions by studying the functional and structural diversity of RecA enzymes. In SPECIFIC AIM 1 we will compare biochemical and structural properties of divergent members of the RecA family. Target enzymes identified by computational methods will be cloned, expressed and purified. Using high throughput methods, DNA-binding and catalytic properties of each RecA ortholog will be determined. Variations in biochemical properties will be correlated with Phylogenetic and/or predicted structural variations within the RecA enzyme family. RecA orthologs representing distinct Phylogenetic and/or biochemical classes will be crystallized in the presence/absence of bound nucleotide, polynucleotide, and mediator protein ligands, and their high resolution X-ray structures will be determined. In SPECIFIC AIM 2 we will study the allosteric mechanisms of divergent RecA enzymes. The roles of key amino acid residues in the induction of the high-affinity ssDNA-binding state will be determined for selected RecA orthologs. The ability of cognate recombination mediator proteins (RMPs) to induce high-affinity RecA-ssDNA binding will also be examined in targeted systems.
同源重组双链断裂修复(DSBR)修复电离辐射产生的双链断裂,这种DNA修复过程从噬菌体到人类是保守的。在所有生物体中,同源DSBR需要大肠杆菌RecA蛋白的同源物的DNA链交换活性。RecA家族是序列保守性最高的DNA修复蛋白家族,在促进同源重组和DSBR交易中表现出较强的全局结构和功能保守性。尽管如此,可获得生化数据的RecAs在DNA结合特性、催化作用和变构机制方面表现出惊人的多样性,而其他RecAs似乎是专门的重组介质。这种多样性/专门化是否反映了RecA功能的不同进化路径?此外,RecA生物化学多样性/专门化在多大程度上反映了环境对宿主生物DNA重组和修复系统的要求?本项目拟通过研究RecA酶的功能和结构多样性来解决这些问题。在SPECIFIC AIM 1中,我们将比较RecA家族不同成员的生化和结构特性。通过计算方法鉴定的目标酶将被克隆、表达和纯化。使用高通量方法,每个RecA同源物的dna结合和催化性能将被确定。生物化学特性的变化将与系统发育和/或

项目成果

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SCOTT W MORRICAL其他文献

SCOTT W MORRICAL的其他文献

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{{ truncateString('SCOTT W MORRICAL', 18)}}的其他基金

Homology Directed Repair
同源定向修复
  • 批准号:
    8327274
  • 财政年份:
    2004
  • 资助金额:
    $ 19.55万
  • 项目类别:
Homology Directed Repair
同源定向修复
  • 批准号:
    8381905
  • 财政年份:
    2004
  • 资助金额:
    $ 19.55万
  • 项目类别:
Homology Directed Repair
同源定向修复
  • 批准号:
    8725060
  • 财政年份:
    2004
  • 资助金额:
    $ 19.55万
  • 项目类别:
Homology Directed Repair
同源定向修复
  • 批准号:
    8543550
  • 财政年份:
    2004
  • 资助金额:
    $ 19.55万
  • 项目类别:
Homology Directed Repair
同源定向修复
  • 批准号:
    7992616
  • 财政年份:
    2004
  • 资助金额:
    $ 19.55万
  • 项目类别:
ASSEMBLY AND ACTIVATION OF ENZYME SSDNA COMPLEXES
SSDNA 酶复合物的组装和激活
  • 批准号:
    2396916
  • 财政年份:
    1996
  • 资助金额:
    $ 19.55万
  • 项目类别:
Assembly and Activation of Enzyme-ssDNA Complexes
酶-ssDNA复合物的组装和激活
  • 批准号:
    6544460
  • 财政年份:
    1993
  • 资助金额:
    $ 19.55万
  • 项目类别:
Assembly and Activation of Enzyme-ssDNA Complexes
酶-ssDNA复合物的组装和激活
  • 批准号:
    6920725
  • 财政年份:
    1993
  • 资助金额:
    $ 19.55万
  • 项目类别:
Assembly and Activation of Enzyme-ssDNA Complexes
酶-ssDNA复合物的组装和激活
  • 批准号:
    8018659
  • 财政年份:
    1993
  • 资助金额:
    $ 19.55万
  • 项目类别:
ASSEMBLY AND ACTIVATION OF ENZYME-SSDNA COMPLEXES
酶-SSDNA 复合物的组装和激活
  • 批准号:
    2691547
  • 财政年份:
    1993
  • 资助金额:
    $ 19.55万
  • 项目类别:

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