Reconstitution of a flexible SYCP3-DNA fibre suggests a mechanism for SYCP3 coating of the meiotic chromosome axis
Reconstitution of a flexible SYCP3-DNA fibre suggests a mechanism for SYCP3 coating of the meiotic chromosome axis
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DOI：
10.1101/369439
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发表时间：
2018-07
期刊：
影响因子：
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通讯作者：
D. Bollschweiler;L. Radu;J. Plitzko;R. Henderson;I. Mela;L. Pellegrini
中科院分区：
文献类型：
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作者：
D. Bollschweiler;L. Radu;J. Plitzko;R. Henderson;I. Mela;L. Pellegrini
联会复合体（SC）在减数分裂交换过程中保持同源染色体紧密排列。SC形成的标志是其蛋白质组分SYCP 3在染色体轴上的存在。随着SC组装的进展，SYCP3沉积在同源对的两个轴上，形成成熟SC的三方结构中的侧向元件（LE）。我们已经使用冷冻电子断层扫描和原子力显微镜来研究SYCP3纤维的组装和DNA结合的机制。我们发现，三维结构的纤维是建立在一个高度不规则的安排SYCP3分子显示非常有限的局部几何形状。SYCP3分子之间的相互作用是由蛋白质的内在无序尾部驱动的，螺旋核心之间没有接触，导致柔性纤维组装。我们证明了SYCP3纤维可以与DNA进行广泛的相互作用，这表明了纤维内DNA掺入的有效机制。总之，我们的研究结果表明，在染色体轴上沉积后，SYCP3通过聚合成纤维而扩散，该纤维通过DNA结合固定在染色体表面。SYCP3包被染色体轴的结果层可能为LE组装在减数分裂前期提供了结构基础。
The synaptonemal complex (SC) keeps homologous chromosomes in close alignment during meiotic crossover. A hallmark of SC formation is the presence of its protein component SYCP3 on the chromosome axis. As SC assembly progresses, SYCP3 is deposited on both axes of the homologue pair, forming the lateral element (LE) in the tripartite structure of the mature SC. We have used cryo-electron tomography and atomic force microscopy to study the mechanism of assembly and DNA binding of the SYCP3 fibre. We find that the three-dimensional architecture of the fibre is built on a highly irregular arrangement of SYCP3 molecules displaying very limited local geometry. Interaction between SYCP3 molecules is driven by the intrinsically disordered tails of the protein, with no contact between the helical cores, resulting in a flexible fibre assembly. We demonstrate that the SYCP3 fibre can engage in extensive interactions with DNA, indicative of an efficient mechanism for incorporation of DNA within the fibre. Taken together, our findings suggest that, upon deposition on the chromosome axis, SYCP3 spreads by polymerising into a fibre that is fastened to the chromosome surface via DNA binding. The resulting layer of SYCP3 coating the chromosome axis might provide a structural basis for LE assembly in meiotic prophase.