Howard Hughes Medical Institute and Departments of Microbiology, Molecular and Cellular Biology, and Cell Biology and Human Anatomy, University of California Davis, Davis, California, United States of America.
PLoS Genet. 2012 Jun;8(6):e1002790. doi: 10.1371/journal.pgen.1002790. Epub 2012 Jun 28.
The intimate synapsis of homologous chromosome pairs (homologs) by synaptonemal complexes (SCs) is an essential feature of meiosis. In many organisms, synapsis and homologous recombination are interdependent: recombination promotes SC formation and SCs are required for crossing-over. Moreover, several studies indicate that initiation of SC assembly occurs at sites where crossovers will subsequently form. However, recent analyses in budding yeast and fruit fly imply a special role for centromeres in the initiation of SC formation. In addition, in budding yeast, persistent SC-dependent centromere-association facilitates the disjunction of chromosomes that have failed to become connected by crossovers. Here, we examine the interplay between SCs, recombination, and centromeres in a mammal. In mouse spermatocytes, centromeres do not serve as SC initiation sites and are invariably the last regions to synapse. However, centromeres are refractory to de-synapsis during diplonema and remain associated by short SC fragments. Since SC-dependent centromere association is lost before diakinesis, a direct role in homolog segregation seems unlikely. However, post-SC disassembly, we find evidence of inter-centromeric connections that could play a more direct role in promoting homolog biorientation and disjunction. A second class of persistent SC fragments is shown to be crossover-dependent. Super-resolution structured-illumination microscopy (SIM) reveals that these structures initially connect separate homolog axes and progressively diminish as chiasmata form. Thus, DNA crossing-over (which occurs during pachynema) and axis remodeling appear to be temporally distinct aspects of chiasma formation. SIM analysis of the synapsis and crossover-defective mutant Sycp1⁻/⁻ implies that SCs prevent unregulated fusion of homolog axes. We propose that SC fragments retained during diplonema stabilize nascent bivalents and help orchestrate local chromosome reorganization that promotes centromere and chiasma function.
同源染色体对（同源物）通过联会复合体（SCs）的紧密联会是减数分裂的一个基本特征。在许多生物体中，联会和同源重组是相互依赖的：重组促进 SC 的形成，而 SC 是交叉形成所必需的。此外，几项研究表明，SC 组装的起始发生在随后会形成交叉的位置。然而，芽殖酵母和果蝇的最近分析表明着丝粒在 SC 形成的起始中具有特殊作用。此外，在芽殖酵母中，持续的依赖于 SC 的着丝粒关联有助于分离未能通过交叉连接的染色体。在这里，我们在哺乳动物中研究了 SC、重组和着丝粒之间的相互作用。在小鼠精母细胞中，着丝粒不作为 SC 起始位点，并且始终是最后一个联会的区域。然而，在双线期，着丝粒对抗去联会，并且仍然通过短的 SC 片段连接。由于 SC 依赖性着丝粒关联在减数分裂前期丢失，因此直接参与同源物分离似乎不太可能。然而，在 SC 解体后，我们发现存在着丝粒间连接的证据，这可能在促进同源物二分体化和分离中发挥更直接的作用。第二类持续的 SC 片段被证明是依赖于交叉的。超分辨率结构照明显微镜（SIM）显示，这些结构最初连接单独的同源轴，并且随着交叉形成而逐渐减少。因此，DNA 交叉（发生在粗线期）和轴重塑似乎是交叉形成的时间上不同的方面。对联会和交叉缺陷突变体 Sycp1⁻/⁻的 SIM 分析表明，SC 阻止同源轴的不受控制融合。我们提出，在双线期保留的 SC 片段稳定新生的二价体，并有助于协调促进着丝粒和交叉功能的局部染色体重排。
