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纺锤体检查点蛋白 Mad2 在酿酒酵母减数分裂 I 的前期和中期调节 APC/C 的活性。

The spindle checkpoint protein Mad2 regulates APC/C activity during prometaphase and metaphase of meiosis I in Saccharomyces cerevisiae.

机构信息

Department of Biology, Indiana University, Bloomington, IN 47405, USA.

出版信息

Mol Biol Cell. 2011 Aug 15;22(16):2848-61. doi: 10.1091/mbc.E11-04-0378. Epub 2011 Jun 22.

DOI:10.1091/mbc.E11-04-0378
PMID:21697504
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3154881/
Abstract

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 APC(Cdc20). 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 APC(Cdc20) and APC(Ama1) are prematurely active, and meiosis I and meiosis II events occur in a single meiotic division. We show that Mad2 indirectly regulates APC(Ama1) activity by decreasing APC(Cdc20) 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.

摘要

在许多真核生物中，纺锤体检验点蛋白 Mad2 的破坏会导致减数分裂 I 中不分离的增加，这表明 Mad2 在确保减数分裂中染色体的忠实分离方面具有保守作用。为了表征 Mad2 的减数分裂功能，我们分析了经历减数分裂的单个出芽酵母细胞。我们发现 Mad2 通过调节 APC(Cdc20)的活性来设定减数分裂 I 的持续时间。在没有 Mad2 的情况下，大多数细胞都会经历两次减数分裂，但 securin，即 APC/C 的底物，会过早降解，并且前期 I/中期 I 会加速。一些 mad2Δ细胞的减数分裂细胞周期事件调控失常，会进行一次异常的分裂，其中姐妹染色单体分离。在这些细胞中，APC(Cdc20)和 APC(Ama1)都过早地活跃，减数分裂 I 和减数分裂 II 事件发生在一次减数分裂中。我们表明 Mad2 通过降低 APC(Cdc20)的活性来间接调节 APC(Ama1)的活性。我们提出 Mad2 是一个重要的减数分裂细胞周期调节剂，它确保 APC/C 底物的及时降解和减数分裂的适当协调。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8883/3154881/901eb842f993/2848fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8883/3154881/3fb4aed27e81/2848fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8883/3154881/5de0b2e7b30f/2848fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8883/3154881/5e6dcc161560/2848fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8883/3154881/7a8d4f32a8eb/2848fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8883/3154881/adc43506f565/2848fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8883/3154881/d33ab4cce17e/2848fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8883/3154881/02fcd8af5ebb/2848fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8883/3154881/901eb842f993/2848fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8883/3154881/3fb4aed27e81/2848fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8883/3154881/5de0b2e7b30f/2848fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8883/3154881/5e6dcc161560/2848fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8883/3154881/7a8d4f32a8eb/2848fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8883/3154881/adc43506f565/2848fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8883/3154881/d33ab4cce17e/2848fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8883/3154881/02fcd8af5ebb/2848fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8883/3154881/901eb842f993/2848fig8.jpg

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