HAL-2 promotes homologous pairing during Caenorhabditis elegans meiosis by antagonizing inhibitory effects of synaptonemal complex precursors.
HAL-2 promotes homologous pairing during Caenorhabditis elegans meiosis by antagonizing inhibitory effects of synaptonemal complex precursors.
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HAL-2通过拮抗突触复合体前体的抑制作用，促进秀丽隐杆线虫减数症期间的同源配对。
DOI：
10.1371/journal.pgen.1002880
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Villeneuve AM
中科院分区：
文献类型：
--
作者：
Zhang W;Miley N;Zastrow MS;MacQueen AJ;Sato A;Nabeshima K;Martinez-Perez E;Mlynarczyk-Evans S;Carlton PM;Villeneuve AM
在减数分裂过程中，染色体与它们的同源配对配对，并通过联会复合体(SC)的组装来稳定这种配对。由于SC是协同组装的，但与同源性无关，配对和SC组装必须紧密协调。我们发现HAL-2是这种协调中的关键介质，表明HAL-2在很大程度上通过防止SC前体(SYP蛋白)的有害影响促进配对。HAL-2突变体无法建立配对，并且缺乏由配对中心(PC)介导的多个染色体运动标记，PC是通过核膜跨越复合体将染色体与细胞质微管连接起来的染色体位置。此外，在Hal-2突变体中，SYP蛋白在单个未配对的染色体上不适当地加载，在Hal-2；SYP双突变体中，依赖PC的运动和功能的标志被恢复。这些和其他数据表明，SYP蛋白可以阻碍配对，HAL-2主要但不是唯一地通过对抗这种抑制来促进配对，从而激活和调节PC功能。当SC组装被阻止时，HAL-2集中在生殖细胞核质中，并与SYP蛋白在核聚集体中共存。我们认为，HAL-2的功能是在SC组装许可之前守护SYP蛋白，防止SC前体与染色体之间的不及时相互作用，并允许足够的前体积累，以便在同源性验证后快速合作组装。为了在有性繁殖过程中成功分离同源染色体，同源染色体必须首先识别并与正确的伴侣配对。此外，许多生物通过组装称为联会复合体(SC)的高度有序的结构来稳定和维持成对的同系物之间的比对。配对和突触必须紧密协调，以确保SC组装只以一种富有成效的方式发生，将正确排列的同源染色体的轴连接起来。在这项工作中，我们确定HAL-2，一种集中在生殖细胞核质中的蛋白质，是调节这种协调的关键角色。我们发现SC的前体有可能抑制同源配对，干扰SC正常起稳定作用的过程。此外，我们还表明，HAL-2主要通过抵消SC前体的这些有害抑制效应来促进同源配对和相关的染色体移动。我们的数据表明，HAL-2用于防止SC前体在SC组装许可之前与染色体的不适当关联，我们认为HAL-2可能使前体以一种允许同源性验证后快速、合作的SC组装的方式积累。
During meiosis, chromosomes align with their homologous pairing partners and stabilize this alignment through assembly of the synaptonemal complex (SC). Since the SC assembles cooperatively yet is indifferent to homology, pairing and SC assembly must be tightly coordinated. We identify HAL-2 as a key mediator in this coordination, showing that HAL-2 promotes pairing largely by preventing detrimental effects of SC precursors (SYP proteins). hal-2 mutants fail to establish pairing and lack multiple markers of chromosome movement mediated by pairing centers (PCs), chromosome sites that link chromosomes to cytoplasmic microtubules through nuclear envelope-spanning complexes. Moreover, SYP proteins load inappropriately along individual unpaired chromosomes in hal-2 mutants, and markers of PC-dependent movement and function are restored in hal-2; syp double mutants. These and other data indicate that SYP proteins can impede pairing and that HAL-2 promotes pairing predominantly but not exclusively by counteracting this inhibition, thereby enabling activation and regulation of PC function. HAL-2 concentrates in the germ cell nucleoplasm and colocalizes with SYP proteins in nuclear aggregates when SC assembly is prevented. We propose that HAL-2 functions to shepherd SYP proteins prior to licensing of SC assembly, preventing untimely interactions between SC precursors and chromosomes and allowing sufficient accumulation of precursors for rapid cooperative assembly upon homology verification. For successful segregation of homologous chromosomes during sexual reproduction, homologs must first identify and pair with their correct partners. Further, many organisms stabilize and maintain alignment between paired homologs through assembly of a highly ordered structure known as the synaptonemal complex (SC). Pairing and synapsis must be tightly coordinated to ensure that SC assembly only occurs in a productive manner, linking the axes of correctly aligned homologous chromosomes. In this work, we identify HAL-2, a protein that concentrates in the nucleoplasm of germ cells, as a key player in mediating this coordination. We find that precursors of the SC have the potential to inhibit homolog pairing, interfering with the very process that the SC normally serves to stabilize. Moreover, we show that HAL-2 promotes homolog pairing and associated chromosome movement primarily by counteracting these detrimental inhibitory effects of SC precursors. Our data suggest that HAL-2 serves to prevent inappropriate association of SC precursors with chromosomes prior to licensing of SC assembly, and we propose that HAL-2 may enable precursors to accumulate in a manner that allows rapid, cooperative SC assembly upon homology verification.
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影响因子：
10.5
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Martinez-Perez, E;Villeneuve, AM
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