The spindle checkpoint, APC/C(Cdc20), and APC/C(Cdh1) play distinct roles in connecting mitosis to S phase.
The spindle checkpoint, APC/C(Cdc20), and APC/C(Cdh1) play distinct roles in connecting mitosis to S phase.
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DOI：
10.1083/jcb.201211019
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发表时间：
2013-06-24
期刊：
影响因子：
--
通讯作者：
Wolthuis R
中科院分区：
文献类型：
--
作者：
Clijsters L;Ogink J;Wolthuis R
纺锤体检查点APC/C-Cdc 20和APC/C-Cdh 1依次作用，将双生蛋白和细胞周期蛋白B1的消失与Cdt 1和Cdc 6的峰值连接起来。DNA复制依赖于Cdt 1和Cdc 6的先前许可事件。在动物细胞中，Cdt 1抑制剂geminin和有丝分裂细胞周期蛋白活性阻止了S期后但有丝分裂前的再授权。在这里，我们表明，geminin，像细胞周期蛋白B1和securin，是一个真正的纺锤体检查点和APC/CCdc 20的目标。细胞周期蛋白B1和geminin在中期同时降解，这指导Cdt 1积累分离的姐妹染色单体。APC/CCDh 1的随后激活导致Cdc 6的降解，而Cdt 1则以复制偶联的方式变得不稳定。在有丝分裂中，纺锤体检查点支持Cdt 1积累，其促进S期开始。我们的结论是，纺锤体检查点，APC/CCdc 20，和APC/CCDh 1的行为，以确保许可抑制剂的消失正好与Cdt 1和Cdc 6的峰值相吻合。而细胞周期进入静止需要Cdc 6再合成，我们的研究结果表明，增殖细胞使用的时间窗口在有丝分裂，Cdc 6降解之前，作为一个更早的机会，直接S期。
The spindle checkpoint, APC/C-Cdc20, and APC/C-Cdh1 act successively to connect disappearance of geminin and cyclin B1 to a peak of Cdt1 and Cdc6. DNA replication depends on a preceding licensing event by Cdt1 and Cdc6. In animal cells, relicensing after S phase but before mitosis is prevented by the Cdt1 inhibitor geminin and mitotic cyclin activity. Here, we show that geminin, like cyclin B1 and securin, is a bona fide target of the spindle checkpoint and APC/CCdc20. Cyclin B1 and geminin are degraded simultaneously during metaphase, which directs Cdt1 accumulation on segregating sister chromatids. Subsequent activation of APC/CCdh1 leads to degradation of Cdc6 well before Cdt1 becomes unstable in a replication-coupled manner. In mitosis, the spindle checkpoint supports Cdt1 accumulation, which promotes S phase onset. We conclude that the spindle checkpoint, APC/CCdc20, and APC/CCdh1 act successively to ensure that the disappearance of licensing inhibitors coincides exactly with a peak of Cdt1 and Cdc6. Whereas cell cycle entry from quiescence requires Cdc6 resynthesis, our results indicate that proliferating cells use a window of time in mitosis, before Cdc6 is degraded, as an earlier opportunity to direct S phase.
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DOI：
10.1083/jcb.200403106
发表时间：
2004-05-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Melixetian M;Ballabeni A;Masiero L;Gasparini P;Zamponi R;Bartek J;Lukas J;Helin K
通讯作者：
Helin K
DOI：
10.1073/pnas.1106136108
发表时间：
2011-06-14
影响因子：
11.1
作者：
Emanuele, Michael J.;Ciccia, Alberto;Elledge, Stephen J.
通讯作者：
Elledge, Stephen J.
影响因子：
11.4
作者：
Ballabeni, A;Melixetian, M;Helin, K
通讯作者：
Helin, K
影响因子：
7.8
作者：
Hagting, Anja;Den Elzen, Nicole;Vodermaier, Hartmut C;Waizenegger, Irene C;Peters, Jan-Michael;Pines, Jonathon
通讯作者：
Pines, Jonathon
影响因子：
21.3
作者：
Li, A;Blow, JJ
通讯作者：
Blow, JJ