Sfr1的CDK磷酸化会下调Rad51在减数分裂后期同源侵袭中的功能。

IF 9.4 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY EMBO Journal Pub Date : 2024-10-01 Epub Date: 2024-08-22 DOI:10.1038/s44318-024-00205-2
Inés Palacios-Blanco, Lucía Gómez, María Bort, Nina Mayerová, Silvia Bágeľová Poláková, Cristina Martín-Castellanos
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引用次数: 0

摘要

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,从而促进染色体的忠实分离。我们利用裂殖酵母以及生物化学、遗传学和细胞学方法,研究了 CDK(依赖细胞周期蛋白的激酶)在控制 Swi5-Sfr1 过程中的作用,Swi5-Sfr1 是一种 Rad51 重组酶辅助因子,在重组过程中参与同源染色体的侵入。我们发现 Sfr1 是 CDK 的靶标,它的磷酸化下调了 Swi5-Sfr1 在减数分裂前期的功能。表达磷酸化拟态 sfr1-7D 突变体可抑制 Rad51 的结合及其强大的染色体负载,从而降低同源染色体间的重组。另一方面,不可磷酸化的 sfr1-7A 突变体改变了 Rad51 在前期后期的动态变化,当与 dbl2 缺失突变体结合时,会加剧染色质分离缺陷和 Rad51 保留。我们认为 Sfr1 磷酸化抑制是一种新的细胞周期依赖性机制,它能确保重组中间体的及时解决和染色体成功分配到配子中。此外,Sfr1的N端无序部分是一个进化保守的特征,它是协调这种磷酸化调控、蛋白质定位和稳定性的调控平台,其中几个CDK位点和调控序列是保守的。
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CDK phosphorylation of Sfr1 downregulates Rad51 function in late-meiotic homolog invasions.

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.

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来源期刊
EMBO Journal
EMBO Journal 生物-生化与分子生物学
CiteScore
18.90
自引率
0.90%
发文量
246
审稿时长
1.5 months
期刊介绍: The EMBO Journal has stood as EMBO's flagship publication since its inception in 1982. Renowned for its international reputation in quality and originality, the journal spans all facets of molecular biology. It serves as a platform for papers elucidating original research of broad general interest in molecular and cell biology, with a distinct focus on molecular mechanisms and physiological relevance. With a commitment to promoting articles reporting novel findings of broad biological significance, The EMBO Journal stands as a key contributor to advancing the field of molecular biology.
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