Laboratory of Chromosome Biology, Max Planck Institute of Biochemistry, Martinsried, Germany.
EMBO J. 2023 Oct 16;42(20):e114288. doi: 10.15252/embj.2023114288. Epub 2023 Sep 20.
Genome haploidization at meiosis depends on two consecutive nuclear divisions, which are controlled by an oscillatory system consisting of Cdk1-cyclin B and the APC/C bound to the Cdc20 activator. How the oscillator generates exactly two divisions has been unclear. We have studied this question in yeast where exit from meiosis involves accumulation of the APC/C activator Ama1 at meiosis II. We show that inactivation of the meiosis I-specific protein Spo13/MEIKIN results in a single-division meiosis due to premature activation of APC/C . In the wild type, Spo13 bound to the polo-like kinase Cdc5 prevents Ama1 synthesis at meiosis I by stabilizing the translational repressor Rim4. In addition, Cdc5-Spo13 inhibits the activity of Ama1 by converting the B-type cyclin Clb1 from a substrate to an inhibitor of Ama1. Cdc20-dependent degradation of Spo13 at anaphase I unleashes a feedback loop that increases Ama1's synthesis and activity, leading to irreversible exit from meiosis at the second division. Thus, by repressing the exit machinery at meiosis I, Cdc5-Spo13 ensures that cells undergo two divisions to produce haploid gametes.
减数分裂中的基因组单倍体化依赖于两个连续的核分裂，这两个分裂由一个由 Cdk1-cyclin B 和 APC/C 组成的振荡器控制，该振荡器与结合到 Cdc20 激活剂的 APC/C 结合。振荡器如何产生恰好两个分裂一直不清楚。我们在酵母中研究了这个问题，其中减数分裂的退出涉及 APC/C 激活剂 Ama1 在减数分裂 II 中的积累。我们表明，减数分裂 I 特异性蛋白 Spo13/MEIKIN 的失活会导致单分裂减数分裂，因为 APC/C 的过早激活。在野生型中，与 polo 样激酶 Cdc5 结合的 Spo13 通过稳定翻译抑制剂 Rim4 来防止减数分裂 I 中 Ama1 的合成。此外，Cdc5-Spo13 通过将 B 型细胞周期蛋白 Clb1 从底物转化为 Ama1 的抑制剂来抑制 Ama1 的活性。在后期 I 时 Cdc20 依赖性降解 Spo13 释放出一个反馈回路，增加 Ama1 的合成和活性，导致在第二次分裂时不可逆地退出减数分裂。因此，通过在减数分裂 I 时抑制退出机制，Cdc5-Spo13 确保细胞经历两次分裂以产生单倍体配子。
