School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea.
Institute of Microbiology, Seoul National University, Seoul 08826, Republic of Korea.
Sci Adv. 2020 Feb 7;6(6):eaay2669. doi: 10.1126/sciadv.aay2669. eCollection 2020 Feb.
Homologous recombination is exquisitely activated only during specific cell phases. In the G phase, homologous recombination activity is completely suppressed. According to previous reports, the activation of homologous recombination during specific cell phases depends on the kinase activity of cyclin-dependent kinase 1 (CDK1). However, the precise regulatory mechanism and target substrates of CDK1 for this regulation have not been completely determined. Here, we report that the budding yeast CDK1, Cdc28, phosphorylates the major homologous recombination regulators Rad51 and Rad52. This phosphorylation occurs in the G/M phase by Cdc28 in combination with G/M phase cyclins. Nonphosphorylatable mutations in Rad51 and Rad52 impair the DNA binding affinity of Rad51 and the affinity between Rad52 rings that leads to their interaction. Collectively, our data provide detailed insights into the regulatory mechanism of cell cycle-dependent homologous recombination activation in eukaryotic cells.
同源重组仅在特定的细胞阶段被高度激活。在 G 期，同源重组活性完全被抑制。根据之前的报道，同源重组在特定细胞阶段的激活依赖于细胞周期蛋白依赖性激酶 1（CDK1）的激酶活性。然而，CDK1 用于这种调节的精确调控机制和靶底物尚未完全确定。在这里，我们报告说，芽殖酵母 CDK1（Cdc28）磷酸化主要的同源重组调节剂 Rad51 和 Rad52。这种磷酸化是由 Cdc28 与 G1/M 期细胞周期蛋白结合在 G1/M 期发生的。Rad51 和 Rad52 中的非磷酸化突变会损害 Rad51 的 DNA 结合亲和力以及 Rad52 环之间的亲和力，从而导致它们相互作用。总的来说，我们的数据提供了对真核细胞中细胞周期依赖性同源重组激活的调控机制的详细了解。
