植物减数分裂特异的CDC20.1调控染色体分离的分子机制

Meiosis is essential for sexual reproduction in eukaryotes. Chromosome segregation is one of key events to ensure successful completion of meiosis. Unlike mitosis with one cellular division following DNA replication once, meiosis takes one DNA replication by two successive nuclear and cellular divisions. The second chromosome segregation is occurred between sister chromatids, which is similar between mitosis and meiosis. Anaphase Promoting Complex (APC) is E3 ubiquitin ligase and plays important roles in regulating mitotic cell cycle progression, but their role in meiosis is unclear. Our previous studies demonstrated that three subunit of APCs may participate in meiosis. It is known that normal APC activity requires activator, like CDC20. Arabidopsis has five copies (CDC20.1-5). Our meiocytes transcriptome showed that CDC20.1 is specifically expressed, but not others. Further functional characterization demonstrated that CDC20.1 is only required for meiotic chromosome segregation. However, molecular mechanism of CDC20.1 in meiosis and its relationship with APC are unknown. Building on the previous results, this project will fully utilize molecular cell biology and genetics, biochemistry and proteomics, to investigate the molecular mechanism of CDC20.1 in regulating meiotic chromosome segregation. Given mechanisms of meiosis are highly conserved between plants and animals, the results will provide a theoretical basis not only for genetic manipulation of crops, but also for human reproductive health.

减数分裂是真核生物有性繁殖所必需的环节，染色体分离是保证减数分裂成功的核心事件之一。不同于有丝分裂中DNA复制一次，细胞分裂一次；减数分裂中DNA复制一次，细胞分裂两次（MI和MII）。MII与有丝分裂类似，将姊妹染色单体分开。后期促进复合体（APC）是E3泛素连接酶，主要功能是调节有丝分裂细胞周期，关于在减数分裂中的功能未见报道。我们前期研究表明APC的三个亚基可能参与减数分裂。由于正常APC的功能需要激活因子，如CDC20。拟南芥有5个拷贝，只有CDC20.1在减数分裂细胞特异表达，进一步研究证明CDC20.1只影响减数分裂中染色体分离，但是其作用机制及与APC的关系不清楚。本项目拟综合采用细胞学、生物化学和蛋白组学等手段，深入阐明CDC20.1特异作用减数分裂中染色体分离的分子机制，基于减数分裂在动植物之间的保守性，研究结果能够为动物和人类生殖健康提供重要的借鉴。

减数分裂是真核生物有性繁殖所必需的环节，染色体分离是保证减数分裂成功的核心事件之一。不同于有丝分裂中DNA复制一次，细胞分裂一次；减数分裂中DNA复制一次，细胞分裂两次（MI和MII）。MII与有丝分裂类似，将姊妹染色单体分开。后期促进复合体（APC）是E3泛素连接酶和及共激活因子，主要功能是调节有丝分裂细胞周期，关于在减数分裂中的功能鲜有报道。本研究发现植物减数分裂中期I同源染色体在赤道板上的正确排列和后期分离需要APC/C的激活因子CDC20.1，其调节机制可能通过调节组蛋白的磷酸化，作用纺锤体组装检验点依赖的途径，从而影响纺锤体与动粒的正确结合。同时还揭示了CDC20的两个拷贝是十字花科中15-33百万年之间产生的一对串联重复基因，且两者之间发生了功能分化。相关结果发表在“Plant Cell”。进一步研究鉴定到APC/C的两个亚基APC8和APC13，其突变导致类似cdc20.1的染色体排列异常表型，首次在植物中揭示了APC/C亚基参与调控减数分裂过程中同源二价体的排列和后期分离，相关结果发表在“New Phytologist”。此外，最近的研究还发现APC/C的另外一个共激活因子CCS52同样参与该环节，其作用机制可能通过影响APC/C活性，从而作用底物的降解。以上工作应邀在《The Arabidopsis Book》上撰写专题综述，总结了该领域的最新进展，并包括了以上成果。基于减数分裂在动植物之间的保守性，研究结果能够为动物和人类生殖健康提供重要的借鉴。