Synergistic actions of Rad51 and Rad52 in recombination and DNA repair.
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. They were subsequently shown to be required for spontaneous and induced mitotic recombination, meiotic recombination, and mating-type switching. Human homologues of RAD50, RAD51, RAD52, RAD54 and MRE11 have been identified. Targeted disruption of the murine RAD51 gene results in an embryonic lethal phenotype, indicating that Rad51 protein is required during cell proliferation. 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. As a structural and functional homologue of the RecA protein from Escherichia coli, hRad51 is thought to play a central role in recombination. Yeast Rad51 has been shown to interact with Rad52 protein, as does the human homologue. 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.
Benson
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Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Hertfordshire, UK.
Baumann
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P
West
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SC
D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology*; D004587:Electrophoresis, Agar Gel; D004926:Escherichia coli; D006801:Humans; D011485:Protein Binding; D051135:Rad51 Recombinase; D051721:Rad52 DNA Repair and Recombination Protein; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins
D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; C497197:RAD52 protein, S cerevisiae; C497194:RAD52 protein, human; D051721:Rad52 DNA Repair and Recombination Protein; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; C495151:RAD51 protein, S cerevisiae; C495153:RAD51 protein, human; D051135:Rad51 Recombinase