联会复合体组装、维持与解聚的调控机制

联会复合体在减数分裂前期发生组装起始、结构维持及最后分步解聚的动态变化，其正常形成及调控是减数分裂染色体得以正确分离的关键。研究其调控机制对探索不育、流产、新生儿缺陷等严重生殖问题产生的根源有重要意义。但联会复合体动态变化的调控机制，特别是由非结构性蛋白介导的调控机制，仍有待于阐明。申请人在线虫中发现了一个新型的联会复合体结合蛋白CRA-2，前期研究结果表明CRA-2是一种非结构性联会复合体组分，参与调控联会复合体的动态变化，并对减数分裂染色体精确分离至关重要。本项研究将通过遗传学、细胞生物学、蛋白组学等手段详细剖析CRA-2对减数分裂进程的调控作用及其作用机制。基于前期数据，我们推测CRA-2通过调节联会复合体的动态变化，使其解聚过程得到精确调控，保证了后期染色体的正确重塑和精确分离。该研究有望揭示联会复合体调控的一种重要方式，及对联会复合体动态变化精确调控的生物学意义。

The synaptonemal complex （SC） undergoes a dynamic process of assembly initiation, structure maintenance and the final disassembly during the meiotic prophase. Precise regulation of the SC is critical for the accurate meiotic chromosome segregation. Investigating the regulatory mechanisms of SC dynamics is of great significance for understanding the sources of errors that cause serious reproductive health problems such as infertility, miscarriages and birth defects. However, the regulatory mechanism, especially regulation through non-structural components of the SC, remains to be elucidated. The applicant identified a novel SC-binding protein CRA-2 in nematode C. elegans. Preliminary results show that CRA-2 is a non-structural SC component, regulating SC dynamics, and is crucial for precise meiotic chromosome segregation. This study will systematically dissect the role of CRA-2 in meiotic progression and the underlying mechanisms, by means of genetics, cell biology and proteomics etc. Based on our preliminary data, we hypothesize that CRA-2 is essential for precise SC disassembly by regulating its dynamics, and thus promotes proper chromosome remodeling and segregation. This study is expected to reveal a critical mechanism for the regulation of the SC, as well as its biological significance.