Department of Reproductive Medicine, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, 518036 Shenzhen, China.
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China.
Development. 2019 Dec 2;146(23):dev182519. doi: 10.1242/dev.182519.
Chromosome segregation is driven by separase, activity of which is inhibited by binding to securin and cyclin B1/CDK1. In meiosis, premature separase activity will induce aneuploidy or abolish chromosome segregation owing to the untimely destruction of cohesin. Recently, we have proved that cyclin B2 can compensate for cyclin B1 in CDK1 activation for the oocyte meiosis G2/M transition. In the present study, we identify an interaction between cyclin B2/CDK1 and separase in mouse oocytes. We find that cyclin B2 degradation is required for separase activation during the metaphase I-anaphase I transition because the presence of stable cyclin B2 leads to failure of homologous chromosome separation and to metaphase I arrest, especially in the simultaneous absence of securin and cyclin B1. Moreover, non-phosphorylatable separase rescues the separation of homologous chromosomes in stable cyclin B2-arrested cyclin B1-null oocytes. Our results indicate that cyclin B2/CDK1 is also responsible for separase inhibition via inhibitory phosphorylation to regulate chromosome separation in oocyte meiosis, which may not occur in other cell types.
染色体分离由分离酶驱动，其活性通过与 securin 和 cyclin B1/CDK1 结合而受到抑制。在减数分裂中，由于黏连蛋白的过早破坏，分离酶的过早活性将导致非整倍体或染色体分离的破坏。最近，我们已经证明 cyclin B2 可以在 CDK1 激活中补偿 cyclin B1，从而促进卵母细胞减数分裂 G2/M 转换。在本研究中，我们鉴定了小鼠卵母细胞中 cyclin B2/CDK1 和分离酶之间的相互作用。我们发现，在中期 I-后期 I 转换期间，cyclin B2 的降解对于分离酶的激活是必需的，因为稳定的 cyclin B2 的存在导致同源染色体分离失败和中期 I 阻滞，特别是在 securin 和 cyclin B1 同时缺失的情况下。此外，非磷酸化的分离酶可以挽救稳定的 cyclin B2 阻滞的 cyclin B1 缺失卵母细胞中同源染色体的分离。我们的结果表明，cyclin B2/CDK1 还通过抑制性磷酸化来抑制分离酶，以调节卵母细胞减数分裂中的染色体分离，这在其他细胞类型中可能不会发生。
