Synchronization of interphase events depends neither on mitosis nor on cdk1
Synchronization of interphase events depends neither on mitosis nor on cdk1
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DOI：
10.1091/mbc.e02-12-0850
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发表时间：
2003-09-01
影响因子：
3.3
通讯作者：
Brandis, M
中科院分区：
文献类型：
--
作者：
Laronne, A;Rotkopf, S;Brandis, M
具有条件性 cdk1 突变的人类 HT2-19 细胞在 cdk1 失活后停止分裂，并经历多轮核内复制。我们在此表明，主要细胞周期事件在这些内复制细胞中保持同步。 DNA 复制与间隙期交替，细胞周期特异性细胞周期蛋白 E 表达得以维持。中心体与染色体复制同步复制，产生具有多个中心体的多倍体细胞。中心体迁移是典型的前期事件，也发生在内复制细胞中。与正常分裂的细胞相比，这些事件的发生时间不受 cdk1 失活的影响。相比之下，之前显示依赖于 cdk1 的核纤层破裂不会发生在内复制 HT2-19 细胞中。此外，核层所有其他主要成分（如内核膜蛋白和核孔复合物）的分解似乎也依赖于 cdk1。有趣的是，这些内复制细胞中的 APC/C 泛素连接酶是由 fzr 激活的，而不是由 fzy 激活的。因此，间期事件的振荡独立于 cdk1 和有丝分裂，但可能取决于 APC/C-fzr 活性。
Human HT2-19 cells with a conditional cdk1 mutation stop dividing upon cdk1 inactivation and undergo multiple rounds of endoreplication. We show herein that major cell cycle events remain synchronized in these endoreplicating cells. DNA replication alternates with gap phases and cell cycle-specific cyclin E expression is maintained. Centrosomes duplicate in synchrony with chromosome replication, giving rise to polyploid cells with multiple centrosomes. Centrosome migration, a typical prophase event, also takes place in endoreplicating cells. The timing of these events is unaffected by cdk1 inactivation compared with normally dividing cells. Nuclear lamina breakdown, in contrast, previously shown to be dependent on cdk1, does not take place in endoreplicating HT2-19 cells. Moreover, breakdown of all other major components of the nuclear lamina, like the inner nuclear membrane proteins and nuclear pore complexes, seems also to depend on cdk1. Interestingly, the APC/C ubiquitin ligase is activated in these endoreplicating cells by fzr but not by fzy. The oscillations of interphase events are thus independent of cdk1 and of mitosis but may depend on APC/C-fzr activity.