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首页> 外文期刊>PLoS Genetics >Interaction of yeast Rad51 and Rad52 relieves Rad52-mediated inhibition of de novo telomere addition
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Interaction of yeast Rad51 and Rad52 relieves Rad52-mediated inhibition of de novo telomere addition

机译：酵母Rad51和Rad52的相互作用可缓解Rad52介导的<斜视> de novoh-/斜体>端粒加入

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DNA double-strand breaks (DSBs) are toxic forms of DNA damage that must be repaired to maintain genome integrity. Telomerase can act upon a DSB to create a de novo telomere, a process that interferes with normal repair and creates terminal deletions. We previously identified sequences in Saccharomyces cerevisiae (SiRTAs; Sites of Repair-associated Telomere Addition) that undergo unusually high frequencies of de novo telomere addition, even when the original chromosome break is several kilobases distal to the eventual site of telomerase action. Association of the single-stranded telomere binding protein Cdc13 with a SiRTA is required to stimulate de novo telomere addition. Because extensive resection must occur prior to Cdc13 binding, we utilized these sites to monitor the effect of proteins involved in homologous recombination. We find that telomere addition is significantly reduced in the absence of the Rad51 recombinase, while loss of Rad52, required for Rad51 nucleoprotein filament formation, has no effect. Deletion of RAD52 suppresses the defect of the rad51Δ strain, suggesting that Rad52 inhibits de novo telomere addition in the absence of Rad51. The ability of Rad51 to counteract this effect of Rad52 does not require DNA binding by Rad51, but does require interaction between the two proteins, while the inhibitory effect of Rad52 depends on its interaction with Replication Protein A (RPA). Intriguingly, the genetic interactions we report between RAD51 and RAD52 are similar to those previously observed in the context of checkpoint adaptation. Forced recruitment of Cdc13 fully restores telomere addition in the absence of Rad51, suggesting that Rad52, through its interaction with RPA-coated single-stranded DNA, inhibits the ability of Cdc13 to bind and stimulate telomere addition. Loss of the Rad51-Rad52 interaction also stimulates a subset of Rad52-dependent microhomology-mediated repair (MHMR) events, consistent with the known ability of Rad51 to prevent single-strand annealing.
机译：DNA双链断裂（DSB）是毒性形式的DNA损伤，必须修复以维持基因组完整性。端粒酶可以在DSB上采取行动，以创建DE Novo Telometere，一种干扰正常修复的过程并产生终端缺失。我们之前鉴定了酿酒酵母（Sirtas;修复相关端粒剂的遗址）中鉴定出异常高频率的De Novo端粒体的频率，即使原始染色体突破是几千碱基到最终的端粒酶动作的遗址。需要与SIRTA的单链端粒结合蛋白CDC13的关联是刺激De Novo端粒体的添加。因为在CDC13结合之前必须发生广泛的切除，所以我们使用这些位点来监测蛋白质参与同源重组的效果。我们发现在没有Rad51重组酶的情况下，端粒加入显着降低，同时Rad51核蛋白长丝形成所需的Rad52的丧失没有效果。 Rad52的缺失抑制了RAD51δ应变的缺陷，表明RAD52抑制了在不存在RAD51的情况下的Novo端粒加法。 RAD51抵消这种RAD52效果的能力不需要通过RAD51结合DNA，但是确实需要两种蛋白质之间的相互作用，而RAD52的抑制作用取决于其与复制蛋白A（RPA）的相互作用。有趣的是，我们在Rad51和Rad52之间报告的遗传相互作用与在检查点适应的上下文中的先前观察到的那些类似。强制招募CDC13完全恢复端粒加法在没有RAD51的情况下，表明RAD52通过其与RPA涂覆的单链DNA的相互作用抑制CDC13结合和刺激端粒加入的能力。 RAD51-RAD52相互作用的丧失还刺激了依赖于RAD52依赖性微型学介导的修复（MHMR）事件的子集，与RAD51的已知能力一致，以防止单链退火。

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