The spindle checkpoint protein Mad2 regulates APC/C activity during prometaphase and metaphase of meiosis I in Saccharomyces cerevisiae.
The spindle checkpoint protein Mad2 regulates APC/C activity during prometaphase and metaphase of meiosis I in Saccharomyces cerevisiae.
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DOI：
10.1091/mbc.e11-04-0378
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发表时间：
2011-08-15
影响因子：
3.3
通讯作者：
Lacefield S
中科院分区：
文献类型：
--
作者：
Tsuchiya D;Gonzalez C;Lacefield S
纺锤体检查点蛋白Mad 2通过下调APC/C活性来设定减数分裂I的持续时间，以确保APC/C底物的及时降解。在缺乏Mad 2的情况下，过早的APC/C活性可引起减数分裂细胞周期事件的失调，导致染色体错误分离。在许多真核生物中，纺锤体检查点蛋白Mad 2的破坏导致减数分裂I不分离的增加，这表明Mad 2在确保减数分裂中的染色体分离中具有保守的作用。为了表征Mad 2的减数分裂功能，我们分析了经历减数分裂的单个芽殖酵母细胞。我们发现Mad 2通过调节APCCdc 20的活性来设定减数分裂I的持续时间。在Mad 2的情况下，大多数细胞进行两次减数分裂，但securin，APC/C的底物，过早降解，并加速前中期I/中期I。一些mad 2 Δ细胞具有减数分裂细胞周期事件的错误调节，并且经历单一的异常分裂，其中姐妹染色单体分离。在这些细胞中，APCCdc 20和APCAma 1都是过早活跃的，减数分裂I和减数分裂II事件发生在单个减数分裂中。我们发现Mad 2通过降低APCCdc 20活性间接调节APCAma 1活性。我们认为Mad 2是一个重要的减数分裂细胞周期调节因子，它确保APC/C底物的及时降解和减数分裂的正确编排。
The spindle checkpoint protein Mad2 sets the duration of meiosis I by down-regulating APC/C activity to ensure the timely degradation of APC/C substrates. In the absence of Mad2, premature APC/C activity can cause misregulation of meiotic cell cycle events, resulting in chromosome missegregation. In many eukaryotes, disruption of the spindle checkpoint protein Mad2 results in an increase in meiosis I nondisjunction, suggesting that Mad2 has a conserved role in ensuring faithful chromosome segregation in meiosis. To characterize the meiotic function of Mad2, we analyzed individual budding yeast cells undergoing meiosis. We find that Mad2 sets the duration of meiosis I by regulating the activity of APCCdc20. In the absence of Mad2, most cells undergo both meiotic divisions, but securin, a substrate of the APC/C, is degraded prematurely, and prometaphase I/metaphase I is accelerated. Some mad2Δ cells have a misregulation of meiotic cell cycle events and undergo a single aberrant division in which sister chromatids separate. In these cells, both APCCdc20 and APCAma1 are prematurely active, and meiosis I and meiosis II events occur in a single meiotic division. We show that Mad2 indirectly regulates APCAma1 activity by decreasing APCCdc20 activity. We propose that Mad2 is an important meiotic cell cycle regulator that ensures the timely degradation of APC/C substrates and the proper orchestration of the meiotic divisions.