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Rad52 protein stimulates DNA strand exchange by Rad51 and replication protein A (see comments)

机译:Rad52蛋白通过Rad51和复制蛋白A刺激DNA链交换(请参阅评论)

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摘要

The generation of a double-strand break in the Saccharomyces cerevisiae genome is a potentially catastrophic event that can induce cell-cycle arrest or ultimately result in loss of cell viability. The repair of such lesions is strongly dependent on proteins encoded by the RAD52 epistasis group of genes (RAD50-55, RAD57, MRE11, XRS2), as well as the RFA1 and RAD59 genes. rad52 mutants exhibit the most severe phenotypic defects in double-strand break repair, but almost nothing is known about the biochemical role of Rad52 protein. Rad51 protein promotes DNA strand exchange and acts similarly to RecA protein. Yeast Rad52 protein interacts with Rad51 protein, binds single-stranded DNA and stimulates annealing of complementary single-stranded DNA. We find that Rad52 protein stimulates DNA strand exchange by targeting Rad51 protein to a complex of replication protein A (RPA) with single-stranded DNA. Rad52 protein affects an early step in the reaction, presynaptic filament formation, by overcoming the inhibitory effects of the competitor, RPA. Furthermore, stimulation is dependent on the concerted action of both Rad51 protein and RPA, implying that specific protein-protein interactions between Rad52 protein, Rad51 protein and RPA are required.
机译:酿酒酵母基因组中双链断裂的产生是潜在的灾难性事件,其可以诱导细胞周期停滞或最终导致细胞生存力丧失。此类病变的修复在很大程度上取决于RAD52上位基因组(RAD50-55,RAD57,MRE11,XRS2)以及RFA1和RAD59基因编码的蛋白质。 rad52突变体在双链断裂修复中表现出最严重的表型缺陷,但对Rad52蛋白的生物化学作用几乎一无所知。 Rad51蛋白促进DNA链交换,其作用类似于RecA蛋白。酵母Rad52蛋白与Rad51蛋白相互作用,结合单链DNA,并刺激互补的单链DNA退火。我们发现Rad52蛋白通过将Rad51蛋白靶向复制蛋白A(RPA)与单链DNA的复合体来刺激DNA链交换。 Rad52蛋白通过克服竞争者RPA的抑制作用,影响了反应的早期阶段,突触前丝的形成。此外,刺激依赖于Rad51蛋白质和RPA的协同作用,这意味着Rad52蛋白质,Rad51蛋白质和RPA之间需要特定的蛋白质-蛋白质相互作用。

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