Meiosis is the developmental program that generates gametes. To produce healthy gametes, meiotic recombination creates reciprocal exchanges between each pair of homologous chromosomes that facilitate faithful chromosome segregation. Using fission yeast and biochemical, genetic, and cytological approaches, we have studied the role of CDK (cyclin-dependent kinase) in the control of Swi5-Sfr1, a Rad51-recombinase auxiliary factor involved in homolog invasion during recombination. We show that Sfr1 is a CDK target, and its phosphorylation downregulates Swi5-Sfr1 function in the meiotic prophase. Expression of a phospho-mimetic sfr1-7D mutant inhibits Rad51 binding, its robust chromosome loading, and subsequently decreases interhomolog recombination. On the other hand, the non-phosphorylatable sfr1-7A mutant alters Rad51 dynamics at late prophase, and exacerbates chromatin segregation defects and Rad51 retention observed in dbl2 deletion mutants when combined with them. We propose Sfr1 phospho-inhibition as a novel cell-cycle-dependent mechanism, which ensures timely resolution of recombination intermediates and successful chromosome distribution into the gametes. Furthermore, the N-terminal disordered part of Sfr1, an evolutionarily conserved feature, serves as a regulatory platform coordinating this phospho-regulation, protein localization and stability, with several CDK sites and regulatory sequences being conserved.

中文翻译：

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Sfr1 的 CDK 磷酸化在晚期减数分裂同源物侵袭中下调 Rad51 功能。


减数分裂是产生配子的发育程序。为了产生健康的配子，减数分裂重组在每对同源染色体之间产生相互交换，从而促进忠实的染色体分离。使用裂变酵母和生化、遗传和细胞学方法，我们研究了 CDK（细胞周期蛋白依赖性激酶）在控制 Swi5-Sfr1 中的作用，Swi5-Sfr1 是一种参与重组过程中同源物侵袭的 Rad51-重组酶辅助因子。我们表明 Sfr1 是一个 CDK 靶标，其磷酸化下调了减数分裂前期的 Swi5-Sfr1 功能。磷酸化模拟物 sfr1-7D 突变体的表达抑制 Rad51 结合、其强大的染色体负载，并随后降低同源间重组。另一方面，不可磷酸化的 sfr1-7A 突变体在前期晚期改变了 Rad51 动力学，并加剧了在 dbl2 缺失突变体中观察到的染色质分离缺陷和 Rad51 保留。我们提出 Sfr1 磷酸化抑制作为一种新的细胞周期依赖性机制，可确保及时解决重组中间体并将染色体成功分布到配子中。此外，Sfr1 的 N 末端无序部分是一种进化上保守的特征，可作为协调这种磷酸化调节、蛋白质定位和稳定性的调节平台，几个 CDK 位点和调节序列是保守的。