The Synaptonemal Complex Shapes the Crossover Landscape Through Cooperative Assembly, Crossover Promotion and Crossover Inhibition During Caenorhabditis elegans Meiosis
The Synaptonemal Complex Shapes the Crossover Landscape Through Cooperative Assembly, Crossover Promotion and Crossover Inhibition During Caenorhabditis elegans Meiosis
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DOI：
10.1534/genetics.110.115501
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发表时间：
2010-09-01
期刊：
影响因子：
3.3
通讯作者：
Villeneuve, Anne M.
中科院分区：
文献类型：
--
作者：
Hayashi, Michiko;Mlynarczyk-Evans, Susanna;Villeneuve, Anne M.
联会复合体(Synaptonemal Complex，SC)是一种高度有序的蛋白质结构，在减数分裂前期在对齐的同源染色体之间的界面上组装。Sc已被证明具有稳定同源配对和促进同源交叉(CoS)形成的功能。SC如何提供这些功能以及它是否也在抑制CO形成方面发挥作用一直是一个有争议的问题。在这里，我们通过研究在秀丽线虫减数分裂过程中减少(但不是消除)SC中心区的主要结构成分SYP-1的后果，为SC的组装和功能提供了新的见解。首先，我们发现在RNAi部分耗尽SYP-1后，双CO(DCO)减数分裂产物的发生率增加，这表明SYP-1在通常限制每个减数分裂只有一个同源对交换的机制中发挥了作用。其次，SYP-1 RNAi蠕虫表现出强烈的偏爱CoS发生在X染色体的左半部，并明显偏向于SYP-1蛋白与染色体的左半部相关，这意味着SC在局部促进CoS的功能。SYP-1 RNAi生殖细胞中SYP-1在染色体上的分布为SC中心区的协同组装提供了强有力的佐证，并表明当SYP-1限量存在时，它优先与X染色体结合。此外，观察到的Cos和SYP-1蛋白分布上的偏差支持突触主要在配对中心(PC)附近启动的模型。然而，SC结构的不连续以及PC结合蛋白HIM-8和X染色体相关的SYP-1延伸的局部焦点之间的明显差距允许改进PC在促进突触中的作用的模型。我们的数据表明，CO景观是由SC中心区的三个属性共同塑造的：在CO位点局部发挥作用的CO促进活动，使CO在远离突触起始部位的区域形成CO的合作组装过程，以及限制CO数量的CO抑制作用(S)。
The synaptonemal complex (SC) is a highly ordered proteinaceous structure that assembles at the interface between aligned homologous chromosomes during meiotic prophase. The SC has been demonstrated to function both in stabilization of homolog pairing and in promoting the formation of interhomolog crossovers (COs). How the SC provides these functions and whether it also plays a role in inhibiting CO formation has been a matter of debate. Here we provide new insight into assembly and function of the SC by investigating the consequences of reducing (but not eliminating) SYP-1, a major structural component of the SC central region, during meiosis in Caenorhabditis elegans. First, we find an increased incidence of double CO (DCO) meiotic products following partial depletion of SYP-1 by RNAi, indicating a role for SYP-1 in mechanisms that normally limit crossovers to one per homolog pair per meiosis. Second, syp-1 RNAi worms exhibit both a strong preference for COs to occur on the left half of the X chromosome and a significant bias for SYP-1 protein to be associated with the left half of the chromosome, implying that the SC functions locally in promoting COs. Distribution of SYP-1 on chromosomes in syp-1 RNAi germ cells provides strong corroboration for cooperative assembly of the SC central region and indicates that SYP-1 preferentially associates with X chromosomes when it is present in limiting quantities. Further, the observed biases in the distribution of both COs and SYP-1 protein support models in which synapsis initiates predominantly in the vicinity of pairing centers (PCs). However, discontinuities in SC structure and clear gaps between localized foci of PC-binding protein HIM-8 and X chromosome-associated SYP-1 stretches allow refinement of models for the role of PCs in promoting synapsis. Our data suggest that the CO landscape is shaped by a combination of three attributes of the SC central region: a CO-promoting activity that functions locally at CO sites, a cooperative assembly process that enables CO formation in regions distant from prominent sites of synapsis initiation, and CO-inhibitory role(s) that limit CO number.