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Phosphoregulation of HORMA domain protein HIM-3 promotes asymmetric synaptonemal complex disassembly in meiotic prophase in Caenorhabditis elegans
PLOS Genetics ( IF 4.0 ) Pub Date : 2020-11-11 , DOI: 10.1371/journal.pgen.1008968
Aya Sato-Carlton , Chihiro Nakamura-Tabuchi , Xuan Li , Hendrik Boog , Madison K. Lehmer , Scott C. Rosenberg , Consuelo Barroso , Enrique Martinez-Perez , Kevin D. Corbett , Peter Mark Carlton

In the two cell divisions of meiosis, diploid genomes are reduced into complementary haploid sets through the discrete, two-step removal of chromosome cohesion, a task carried out in most eukaryotes by protecting cohesion at the centromere until the second division. In eukaryotes without defined centromeres, however, alternative strategies have been innovated. The best-understood of these is found in the nematode Caenorhabditis elegans: after the single off-center crossover divides the chromosome into two segments, or arms, several chromosome-associated proteins or post-translational modifications become specifically partitioned to either the shorter or longer arm, where they promote the correct timing of cohesion loss through as-yet unknown mechanisms. Here, we investigate the meiotic axis HORMA-domain protein HIM-3 and show that it becomes phosphorylated at its C-terminus, within the conserved “closure motif” region bound by the related HORMA-domain proteins HTP-1 and HTP-2. Binding of HTP-2 is abrogated by phosphorylation of the closure motif in in vitro assays, strongly suggesting that in vivo phosphorylation of HIM-3 likely modulates the hierarchical structure of the chromosome axis. Phosphorylation of HIM-3 only occurs on synapsed chromosomes, and similarly to other previously-described phosphorylated proteins of the synaptonemal complex, becomes restricted to the short arm after designation of crossover sites. Regulation of HIM-3 phosphorylation status is required for timely disassembly of synaptonemal complex central elements from the long arm, and is also required for proper timing of HTP-1 and HTP-2 dissociation from the short arm. Phosphorylation of HIM-3 thus plays a role in establishing the identity of short and long arms, thereby contributing to the robustness of the two-step chromosome segregation.



中文翻译:

HORMA域蛋白HIM-3的磷酸化促进秀丽隐杆线虫减数分裂前期的不对称突触复合体分解。

在减数分裂的两个细胞分裂中,二倍体基因组通过不连续的两步去除染色体凝聚力而减少为互补的单倍体集,这是大多数真核生物中通过保护着丝粒的凝聚力直至第二次分裂而完成的任务。然而,在没有明确着丝粒的真核生物中,替代策略已被创新。这些最好的发现是在线虫秀丽隐杆线虫中:在单个偏心交叉将染色体分为两个片段或臂后,几种与染色体相关的蛋白质或翻译后修饰被特异地分配给较短或较长的臂,它们通过以下方式促进内聚力损失的正确时机-未知的机制。在这里,我们研究了减数分裂轴HORMA域蛋白HIM-3,并显示它在其C端被相关的HORMA域蛋白HTP-1和HTP-2结合的保守“封闭基序”区域磷酸化。在体外测定中,通过关闭基序的磷酸化消除了HTP-2的结合,这强烈表明体内HIM-3的磷酸化可能会调节染色体轴的层次结构。HIM-3的磷酸化仅发生在突触的染色体上,并且与先前描述的突触复合物的其他磷酸化蛋白类似,在指定交换位点后,短臂受到了限制。HIM-3磷酸化状态的调节是从长臂中适时拆卸突触复合复杂中心元件所必需的,并且还需要从短臂中适当时机进行HTP-1和HTP-2的解离。因此,HIM-3的磷酸化在确定短臂和长臂的身份中起作用,从而有助于两步染色体分离的鲁棒性。

更新日期:2020-11-12
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