Spp1蛋白质作为接头分子联系组蛋白修饰与减数分裂重组起始的三维结构基础

减数分裂同源染色体重组是遗传多样性形成所必须的，其过程起始于程序性DNA双链断裂（DNA double-strand breaks, DSBs）发生。在酵母和哺乳动物细胞中，组蛋白H3第4位赖氨酸的三甲基化（H3K4me3）标记减数分裂重组热点区域。可是一直都不清楚组蛋白甲基化如何与减数分裂DSBs生成相联系。直到最近报道了酿酒酵母蛋白质Spp1通过其N端区域结合H3K4me3和C端区域结合DSBs生成所需的蛋白质Mer2，将染色质袢环上的潜在DSB热点绑定到染色体轴附近，从而利于DSBs发生。然而相关的结构基础与结合机理尚不清楚。本项目拟解析Spp1 N端区域与H3小肽以及Spp1 C端区域与Mer2的复合物三维结构，揭示Spp1识别特定的组蛋白翻译后修饰以及结合Mer2的结构基础。通过本项目的研究将在原子分辨率水平阐明Spp1作为关键接头分子联系组蛋白修饰与减数分裂重组起始的作用机理。

During meiosis, homologous chromosome recombination is needed for the formation of genetic diversity. Meiotic recombination is initiated by the production of programmed DNA double-strand breaks (DSBs). Histone H3 lysine 4 trimethylation (H3K4me3) marks meiotic recombination hotspots in yeast and mammals, but how histone methylation relates to meiotic DSB formation remained unclear for a long time. Spp1 is recently shown in Saccharomyces cerevisiae to tether potential DSB hotspots to chromosome axes, by interacting with both H3K4me3 and Mer2, and then promote meiotic DSB formation. Mer2 is a protein required for DSB formation. However, relatively little is known about the structural basis and interactional mechanism of the Spp1 protein. Our program aims to obtain the three-dimensional complex structures of Spp1 N-terminal region with H3 tail peptide and Spp1 C-terminal region with Mer2, and then elucidate the structural basis of Spp1 recognizing specific histone post-translational modifications and binding with Mer2. Our study will describe the functional mechanism of Spp1, playing a pivotal role in linking histone modification to initiation of meiotic recombination, at atomic-level resolution.