Cyclin A2 modulates kinetochore-microtubule attachment in meiosis II.

Cyclin A2 modulates kinetochore-microtubule attachment in meiosis II.
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DOI:
10.1083/jcb.201607111
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发表时间:
2017-10-02
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Carroll J
Carroll J
中科院分区:
其他
文献类型:
--
作者:
Zhang QH;Yuen WS;Adhikari D;Flegg JA;FitzHarris G;Conti M;Sicinski P;Nabti I;Marangos P;Carroll J

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Cdk调控蛋白周期蛋白A2在雌性减数分裂中的作用及其动力学尚不清楚。Zhang等人的研究表明,与有丝分裂不同,细胞周期蛋白A2在减数分裂II (MII)中期持续存在。细胞周期蛋白A2调节微管稳定性,允许正常的MII纺锤体形成,并防止MII出口的细粒附着和滞后染色体。细胞周期蛋白A2是一个重要的有丝分裂Cdk调控伙伴,协调进入有丝分裂,然后在核膜破裂的前中期被破坏。细胞周期蛋白A2在雌性减数分裂中的作用及其从减数分裂I (MI)到减数分裂II (MII)过渡过程中的动力学尚不清楚。我们发现细胞周期蛋白A2在I前期减少,但在第一次减数分裂后恢复,并且在mii -阻滞的卵母细胞中持续存在,这是中期独有的。小鼠卵母细胞中细胞周期蛋白A2的条件性删除对心肌梗死没有明显的影响,但会导致心肌梗死纺锤体破坏和血小板附着物增加。在MII退出刺激下,滞后染色体显著增加,胞质分裂受到抑制。这些缺陷与MII纺锤体中微管稳定性的增加有关,表明细胞周期蛋白A2通过在MII纺锤体快速形成过程中维持微管动力学来调节MII的保真度。
The role of the Cdk regulatory protein cyclin A2 and its dynamics in female meiosis are unclear. Zhang et al. show that, unlike in mitosis, cyclin A2 persists during metaphase of meiosis II (MII). Cyclin A2 regulates microtubule stability, allows normal MII spindle formation, and prevents merotelic attachments and lagging chromosomes at MII exit. Cyclin A2 is a crucial mitotic Cdk regulatory partner that coordinates entry into mitosis and is then destroyed in prometaphase within minutes of nuclear envelope breakdown. The role of cyclin A2 in female meiosis and its dynamics during the transition from meiosis I (MI) to meiosis II (MII) remain unclear. We found that cyclin A2 decreases in prometaphase I but recovers after the first meiotic division and persists, uniquely for metaphase, in MII-arrested oocytes. Conditional deletion of cyclin A2 from mouse oocytes has no discernible effect on MI but leads to disrupted MII spindles and increased merotelic attachments. On stimulation of exit from MII, there is a dramatic increase in lagging chromosomes and an inhibition of cytokinesis. These defects are associated with an increase in microtubule stability in MII spindles, suggesting that cyclin A2 mediates the fidelity of MII by maintaining microtubule dynamics during the rapid formation of the MII spindle.
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