Synergistic actions of Rad51 and Rad52 in recombination and DNA repair
Synergistic actions of Rad51 and Rad52 in recombination and DNA repair
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作者：
Benson, FE;Baumann, P;West, SC
在酿酒酵母中，基因RAD 51或RAD 52的突变导致遗传重组和双链DNA断裂修复的严重缺陷，这些基因和其他RAD 52上位组（RAD 50，RAD 54，RAD 55，RAD 57，RAD 59，MRE 11和XRS 2）的基因首先通过它们对X射线的敏感性来鉴定（1）。它们随后被证明是自发和诱导的有丝分裂重组、减数分裂重组和交配型转换所需的（在参考文献2中综述）。已经鉴定了RAD 50、RAD 51、RAD 52、RAD 54和MRE 11的人类同源物（3-6）。鼠RAD 51基因的靶向破坏导致胚胎致死表型，表明细胞增殖期间需要Rad 51蛋白（7，8）。生物化学研究表明，人RAD 51编码相对分子量为36，966的蛋白质（hRad 51），其促进ATP依赖性同源配对和DNA链交换（9-11）。作为来自大肠杆菌的RecA蛋白的结构和功能同源物（3，9，12），hRad 51被认为在重组中起核心作用，酵母Rad 51已显示与Rad 52蛋白相互作用（13-15），人类同源物也是如此（16）。在此，我们显示hRad 52刺激hRad 51的同源配对。hRad 52的DNA结合特性表明Rad 52参与Rad 51介导的重组的早期阶段。
In the yeast Saccharomyces cerevisiae, mutations in the genes RAD51 or RAD52 result in severe defects in genetic recombination and the repair of double-strand DNA breaks, These genes, and others of the RAD52 epistasis group (RAD50, RAD54, RAD55 RAD57, RAD59 MRE11 and XRS2), were first identified by their sensitivity to X-rays(1). They were subsequently shown to be required for spontaneous and induced mitotic recombination, meiotic recombination, and mating-type switching (reviewed in ref, 2), Human homologues of RAD50, RAD51, RAD52 RAD54 and MRE11 have been identified(3-6). Targeted disruption of the murine RAD51 gene results in an embryonic lethal phenotype, indicating that Rad51 protein is required during cell proliferation(7,8). Biochemical studies have shown that human RAD51 encodes a protein of relative molecular mass 36,966 (hRad51) that promotes ATP-dependent homologous pairing and DNA strand exchange(9-11), As a structural and functional homologue of the RecA protein from Escherichia coli(3,9,12), hRad51 is thought to play a central role in recombination, Yeast Rad51 has been shown to interact with Rad52 protein(13-15), as does the human homologue(16), Here we show that hRad52 stimulates homologous pairing by hRad51. The DNA-binding properties of hRad52 indicate that Rad52 is involved in an early stage of Rad51-mediated recombination.