State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.
J Cell Biol. 2019 May 6;218(5):1553-1563. doi: 10.1083/jcb.201808088. Epub 2019 Feb 15.
Meiosis with a single round of DNA replication and two successive rounds of chromosome segregation requires specific cyclins associated with cyclin-dependent kinases (CDKs) to ensure its fidelity. But how cyclins control the distinctive meiosis is still largely unknown. In this study, we explored the role of cyclin B3 in female meiosis by generating mutant mice via CRISPR/Cas9. mutant oocytes characteristically arrested at metaphase I (MetI) with normal spindle assembly and lacked enough anaphase-promoting complex/cyclosome (APC/C) activity, which is spindle assembly checkpoint (SAC) independent, to initiate anaphase I (AnaI). Securin siRNA or CDK1 inhibitor supplements rescued the MetI arrest. Furthermore, CCNB3 directly interacts with CDK1 to exert kinase function. Besides, the MetI arrest oocytes had normal development after intracytoplasmic sperm injection (ICSI) or parthenogenetic activation (PA), along with releasing the sister chromatids, which implies that Ccnb3 exclusively functioned in meiosis I, rather than meiosis II. Our study sheds light on the specific cell cycle control of cyclins in meiosis.
有丝分裂仅进行一轮 DNA 复制和两轮连续的染色体分离,需要与细胞周期蛋白依赖性激酶(CDKs)相关的特定细胞周期蛋白来确保其保真度。但是,细胞周期蛋白如何控制独特的减数分裂在很大程度上仍然未知。在这项研究中,我们通过 CRISPR/Cas9 生成突变小鼠,探索了细胞周期蛋白 B3 在雌性减数分裂中的作用。突变的卵母细胞特征性地停滞在第一次减数分裂中期(MetI),纺锤体组装正常,并且缺乏足够的后期促进复合物/周期蛋白(APC/C)活性,这是纺锤体组装检查点(SAC)独立的,无法启动第一次减数分裂后期(AnaI)。Securin siRNA 或 CDK1 抑制剂补充物挽救了 MetI 阻滞。此外,CCNB3 直接与 CDK1 相互作用以发挥激酶功能。此外,经胞质内精子注射(ICSI)或孤雌激活(PA)后,MetI 阻滞的卵母细胞正常发育,并释放姐妹染色单体,这意味着 Ccnb3 专门在减数分裂 I 中发挥作用,而不是在减数分裂 II 中。我们的研究揭示了细胞周期蛋白在减数分裂中特定的细胞周期控制。