Department of Biological Sciences, Vanderbilt University, Nashville, TN, USA.
Department of Biology, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA, USA.
Curr Genet. 2020 Oct;66(5):917-926. doi: 10.1007/s00294-020-01081-z. Epub 2020 May 12.
DNA double-strand break repair allows cells to survive both exogenous and endogenous insults to the genome. In yeast, the recombinases Rad51 and Rad52 are central to multiple forms of homology-dependent repair. Classically, Rad51 and Rad52 are thought to act cooperatively, with formation of the functional Rad51 nucleofilament facilitated by the mediator function of Rad52. Several studies have now identified functions for the interaction between Rad51 and Rad52 that are independent of the mediator function of Rad52 and affect a seemingly diverse array of functions in de novo telomere addition, global chromosome mobility following DNA damage, Rad51 nucleofilament stability, checkpoint adaptation, and microhomology-mediated chromosome rearrangements. Here, we review these functions with an emphasis on our recent discovery that the Rad51-Rad52 interaction influences the probability of de novo telomere addition at sites preferentially targeted by telomerase following a double-strand break (DSB). We present data addressing the prevalence of sites within the yeast genome that are capable of stimulating de novo telomere addition following a DSB and speculate about the potential role such sites may play in genome stability.
DNA 双链断裂修复使细胞能够在基因组受到内外源损伤后存活下来。在酵母中，重组酶 Rad51 和 Rad52 是多种同源依赖性修复形式的核心。经典地，Rad51 和 Rad52 被认为协同作用，Rad52 的中介功能促进功能性 Rad51 核丝的形成。现在有几项研究已经确定了 Rad51 和 Rad52 之间相互作用的功能，这些功能独立于 Rad52 的中介功能，并影响从头端粒添加、DNA 损伤后全球染色体流动性、Rad51 核丝稳定性、检查点适应和微同源介导的染色体重排等一系列看似不同的功能。在这里，我们重点回顾这些功能，特别是我们最近的发现，即 Rad51-Rad52 相互作用影响了在双链断裂 (DSB) 后，端粒酶优先靶向的部位从头添加端粒的概率。我们提供了数据来解决酵母基因组内能够在 DSB 后刺激从头端粒添加的位点的普遍性，并推测了这些位点在基因组稳定性中可能发挥的潜在作用。
