A yeast two-hybrid screen for SYP-3 interactors identifies SYP-4, a component required for synaptonemal complex assembly and chiasma formation in Caenorhabditis elegans meiosis.
A yeast two-hybrid screen for SYP-3 interactors identifies SYP-4, a component required for synaptonemal complex assembly and chiasma formation in Caenorhabditis elegans meiosis.
复制标题
SYP-3相互作用器的酵母两杂交筛选鉴定了SYP-4，这是秀丽隐杆线虫减数分裂中突发型复合物组装和裂痕形成所需的成分。
DOI：
10.1371/journal.pgen.1000669
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发表时间：
2009-10
期刊：
影响因子：
4.5
通讯作者：
Colaiácovo MP
中科院分区：
文献类型：
--
作者：
Smolikov S;Schild-Prüfert K;Colaiácovo MP
同系物间突触复合体（SC）的正确组装是确保精确减数分裂染色体分离的关键。SC是一种从酵母到人类的减数分裂三方结构，由沿染色体轴组装的蛋白质和连接两条染色体轴的中心区域（CR）蛋白质组成。在这里，我们确定SYP-4是秀丽隐杆线虫SC的一个新的结构成分。在酵母双杂交实验中，SYP-4与SYP-3相互作用，SYP-3是SC中CR的组成部分之一，并且在减数分裂期间定位于同源物之间的界面。SYP-4对于SYP-1、SYP-2和SYP-3 CR蛋白在染色体上的定位至关重要，因此在同源染色体间配对相互作用的稳定中起着至关重要的作用。在SYP-4缺失的情况下，如RAD-51病灶所示，重组中间体的水平在中期前期细胞核中升高，交叉重组事件显著减少。在syp-4突变体中观察到的交叉缺失支持染色体不分离水平升高，表现为高胚胎致死率。总之，我们的研究结果表明SYP-4是SC形成的核心参与者，并拓宽了我们对SC结构及其组装的理解。减数分裂是一个由两部分组成的细胞分裂程序，确保形成单倍体配子（例如卵子和精子），然后通过受精重建一个物种的倍性。完成这项任务的关键一步是在减数分裂i期间同源染色体彼此之间的精确分离。这需要在每对同源染色体之间形成至少一个强制性的交叉事件（遗传交换）。在大多数生物体中，所有交叉事件的形成在很大程度上依赖于突触复合体（SC）。在减数分裂前期I，这种“拉链状”结构将同源染色体对保持在一起，交叉重组在完全形成的sc中完成。在这里，我们发现SYP-4是线虫SC的一个新的结构成分。在缺乏它的情况下，SCs无法形成，导致交叉形成的缺乏和染色体分离错误的增加。在酵母双杂交实验中，SYP-4与SC蛋白之一SYP-3相互作用，其在染色体上的定位与SYP-1、SYP-2和SYP-3蛋白相互依赖。因此，在秀丽隐杆线虫减数分裂过程中，SYP-4在产生从酵母到人类普遍存在的超微结构保守的SC中起着关键作用。
The proper assembly of the synaptonemal complex (SC) between homologs is critical to ensure accurate meiotic chromosome segregation. The SC is a meiotic tripartite structure present from yeast to humans, comprised of proteins assembled along the axes of the chromosomes and central region (CR) proteins that bridge the two chromosome axes. Here we identify SYP-4 as a novel structural component of the SC in Caenorhabditis elegans. SYP-4 interacts in a yeast two-hybrid assay with SYP-3, one of components of the CR of the SC, and is localized at the interface between homologs during meiosis. SYP-4 is essential for the localization of SYP-1, SYP-2, and SYP-3 CR proteins onto chromosomes, thereby playing a crucial role in the stabilization of pairing interactions between homologous chromosomes. In the absence of SYP-4, the levels of recombination intermediates, as indicated by RAD-51 foci, are elevated in mid-prophase nuclei, and crossover recombination events are significantly reduced. The lack of chiasmata observed in syp-4 mutants supports the elevated levels of chromosome nondisjunction manifested in high embryonic lethality. Altogether our findings place SYP-4 as a central player in SC formation and broaden our understanding of the structure of the SC and its assembly. Meiosis is a two-part cell division program that ensures the formation of haploid gametes (e.g. eggs and sperm), which can then reconstitute a species' ploidy through fertilization. A critical step towards accomplishing this task is the accurate segregation of homologous chromosomes away from each other during meiosis I. This requires the formation of at least one obligatory crossover event (genetic exchange) between each pair of homologous chromosomes. In most organisms, the formation of all crossover events greatly relies on the synaptonemal complex (SC). This “zipper-like” structure holds the pairs of homologous chromosomes together during meiotic prophase I, and crossover recombination is completed in the context of the fully formed SCs. Here, we identify SYP-4 as a novel structural component of the SC in the nematode C. elegans. In its absence, SCs fail to form, resulting in a lack of crossover formation and increased errors in chromosome segregation. SYP-4 interacts in a yeast two-hybrid assay with SYP-3, one of the SC proteins, and its localization onto chromosomes is interdependent with SYP-1, SYP-2, and SYP-3 proteins. SYP-4 therefore plays a critical role during C. elegans meiosis in generating the ultrastructurally conserved SC that is ubiquitously present from yeast to humans.