Cyclin A2 modulates kinetochore–microtubule attachment in meiosis II
| Autor: | Deepak Adhikari, Marco Conti, Qing-Hua Zhang, Jennifer A. Flegg, John L. Carroll, Ibtissem Nabti, Greg FitzHarris, Wai Shan Yuen, Piotr Sicinski, Petros Marangos |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cyclin A Microtubules Article Mice 03 medical and health sciences Cyclin-dependent kinase Animals Prometaphase Kinetochores Metaphase Mitosis Research Articles reproductive and urinary physiology Mice Knockout biology urogenital system Meiosis II Cell Biology Chromosomes Mammalian Cell biology Meiosis Spindle checkpoint 030104 developmental biology embryonic structures biology.protein Cyclin A2 |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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