Meiotic recombination is triggered by programmed double-strand breaks (DSBs), a subset of these being repaired as crossovers, promoted by eight evolutionarily conserved proteins, named ZMM. Crossover formation is functionally linked to synaptonemal complex (SC) assembly between homologous chromosomes, but the underlying mechanism is unknown. Here we show that Ecm11, a SC central element protein, localizes on both DSB sites and sites that attach chromatin loops to the chromosome axis, which are the starting points of SC formation, in a way that strictly requires the ZMM protein Zip4. Furthermore, Zip4 directly interacts with Ecm11, and point mutants that specifically abolish this interaction lose Ecm11 binding to chromosomes and exhibit defective SC assembly. This can be partially rescued by artificially tethering interaction-defective Ecm11 to Zip4. Mechanistically, this direct connection ensuring SC assembly from CO sites could be a way for the meiotic cell to shut down further DSB formation once enough recombination sites have been selected for crossovers, thereby preventing excess crossovers. Finally, the mammalian ortholog of Zip4, TEX11, also interacts with the SC central element TEX12, suggesting a general mechanism.

中文翻译：

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Zip4 蛋白直接将减数分裂交叉形成与联会复合体组装结合起来

减数分裂重组是由程序性双链断裂 (DSB) 触发的，其中的一个子集被修复为交叉，由八种进化上保守的蛋白质（称为 ZMM）促进。交叉形成在功能上与同源染色体之间的联会复合体 (SC) 组装有关，但其潜在机制尚不清楚。在这里，我们展示了 Ecm11，一种 SC 中心元件蛋白，以严格要求 ZMM 蛋白 Zip4 的方式定位于 DSB 位点和将染色质环连接到染色体轴的位点，这是 SC 形成的起点。此外，Zip4 直接与 Ecm11 相互作用，而专门消除这种相互作用的点突变体会失去 Ecm11 与染色体的结合并表现出有缺陷的 SC 组装。这可以通过人为地将交互缺陷 Ecm11 绑定到 Zip4 来部分挽救。从机制上讲，一旦选择了足够的重组位点进行交叉，这种直接连接确保从 CO 位点组装 SC 可能是减数分裂细胞关闭进一步 DSB 形成的一种方式，从而防止过度的交叉。最后，Zip4 的哺乳动物直系同源物 TEX11 也与 SC 中心元素 TEX12 相互作用，这表明了一种普遍的机制。