减数分裂过程中Spo11核心复合物的结构和功能研究

减数分裂是有性生殖生物所特有的一种细胞分裂方式，其中同源染色体的重组和联会是其最基本特征，拓扑异构酶Spo11切割染色体DNA造成数百个程序性DNA双链断裂(DSBs)启动了减数分裂重组。除高度保守的Spo11蛋白外，酿酒酵母中程序性DSBs的形成还需其他9个成员的共同参与。由于减数分裂只能在体内发生，且存在特异的时空表达，导致人们对减数分裂启动的分子机制知之甚少。本课题从停滞在减数分裂前期的酵母细胞中纯化到了Spo11-Ski8-Rec102-Rec104四元核心复合物，且伴随着ATR/ATRIP的稳定共纯化，暗示ATR参与调控Spo11复合物的组装进而影响减数分裂启动和重组。我们将通过解析不同功能状态的Spo11-Ski8-Rec102 -Rec104四元核心复合物的高分辨冷冻结构，进而阐明Spo11诱导程序性DSBs的产生机制，推进对减数分裂启动的新认识。

Meiosis is a special form of cell division that occurs in sexually reproducing organisms. The recombination between homologous chromosome and synapsis are the most basic features in meiosis. Meiotic recombination is first initiated by hundreds of programmed DNA double strand breaks which is induced by the topisomerase Spo11. Besides the highly conserved Spo11, the formation of programmed DSBs also need other 9 proteins in yeast. People know little about the mechanism of meiotic recombination initiation, as the occurrence of meiosis in vivo and special spatial expression. We purified the Spo11-Ski8-Rec102-Rec104 core complex from the S. cerevisiae which stagnated at the meiosis prophase, also with the stable co-purificaiton of ATR/ATRIP complex. We will futher analyze the cryo-EM of Spo11-Ski8-Rec102-Rec104 core complex under different functional state. Upon the structural and functional characterization of Spo11 core complex, we will reveal the mechanism of programmed DSBs and meiosis initiation.