Checkpoint kinase 1 is essential for meiotic cell cycle regulation in mouse oocytes
Checkpoint kinase 1 is essential for meiotic cell cycle regulation in mouse oocytes
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检查点激酶 1 对于小鼠卵母细胞减数分裂细胞周期调节至关重要
DOI：
10.4161/cc.20279
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发表时间：
2012-05-15
期刊：
影响因子：
4.3
通讯作者：
Sun, Qing-Yuan
中科院分区：
文献类型：
--
作者：
Chen, Lei;Chao, Shi-Bin;Sun, Qing-Yuan
检查点激酶1（Checkpoint kinase 1，Chk 1）在细胞周期检查点中起关键作用，但其在小鼠卵母细胞减数分裂中的作用尚不清楚。本文报道了Chk 1在小鼠卵母细胞减数分裂中的表达、定位及其功能。Chk 1在小鼠卵母细胞的生发泡（GV）至中期II（MII）阶段表达，在前中期I（pro-MI）至MII阶段定位于纺锤体。Chk 1耗竭促进G2/M期转换，而Chk 1过表达抑制G2/M期转换，通过Cdh 1和Cyclin B1的调节，如germinal vesicle breakdown（GVBD）所示。Chk 1耗竭并不影响减数分裂细胞周期的进展后GVBD，但其过表达后GVBD激活纺锤体组装检查点，阻止同源染色体分离，从而阻止卵母细胞在前MI或中期I（MI）阶段。这些结果表明，Chk 1是必不可少的前期I停滞和功能的G2/M检查点的调节在减数分裂卵母细胞。此外，Chk 1过表达影响减数分裂纺锤体组装检查点调控，从而影响染色体分离。
Checkpoint kinase 1 (Chk1) plays key roles in all currently defined cell cycle checkpoints, but its functions in mouse oocyte meiosis remain unclear. In this study, we report the expression, localization and functions of Chk1 in mouse oocyte meiosis. Chk1 was expressed from germinal vesicle (GV) to metaphase II (MII) stages and localized to the spindle from pro-metaphase I (pro-MI) to MII stages in mouse oocytes. Chk1 depletion facilitated the G2/M transition while Chk1 overexpression inhibited the G2/M transition as indicated by germinal vesicle breakdown (GVBD), through regulation of Cdh1 and Cyclin B1. Chk1 depletion did not affect meiotic cell cycle progression after GVBD, but its overexpression after GVBD activated the spindle assembly checkpoint and prevented homologous chromosome segregation, thus arresting oocytes at pro-MI or metaphase I (MI) stages. These results suggest that Chk1 is indispensable for prophase I arrest and functions in G2/M checkpoint regulation in meiotic oocytes. Moreover, Chk1 overexpression affects meiotic spindle assembly checkpoint regulation and thus chromosome segregation.