Temperature-Induced uncoupling of cell cycle regulators.

Temperature-Induced uncoupling of cell cycle regulators.
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温度诱导的细胞周期调节因子解偶联。

DOI:
10.1016/j.ydbio.2020.11.010
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发表时间:
2021-03
影响因子:
2.7
通讯作者:
Wieschaus E
Wieschaus E
中科院分区:
生物学3区
文献类型:
--
作者:
Falahati H;Hur W;Di Talia S;Wieschaus E

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发育的早期阶段涉及复杂的形态变化序列,这些变化既可从一个胚胎复制到另一个胚胎,而且往往对环境变化具有很强的适应性。为了研究重复性和稳健性之间的关系,我们研究了不同温度下果蝇早期胚胎的细胞周期进程。我们的实验表明,虽然细胞周期步骤的细分在很大的温度范围内(5-35°C)是保守的,但各个步骤的相对持续时间随着温度的变化而变化。我们发现,相对于其他细胞周期事件,进入前中期的转变在较低的温度下会延迟,认为它有不同的调节机制。使用体内生物传感器,我们量化了主要有丝分裂激酶CDK1和主要有丝分裂磷酸酶之一PP1的活性比率。比较不同温度下细胞周期转换时间与激活曲线的关系表明,在早期果蝇胚胎中,CDK1的激活推动进入前中期,而不是早期细胞周期事件所必需的。事实上,当CDK1活性被药物抑制时,仍然可以发生染色体凝聚。这些结果表明,不同的激酶对有丝分裂的不同步骤是限速的,认为快速和有序的有丝分裂可能需要强大的相互调节。
The early stages of development involve complex sequences of morphological changes that are both reproducible from embryo to embryo and often robust to environmental variability. To investigate the relationship between reproducibility and robustness we examined cell cycle progression in early Drosophila embryos at different temperatures. Our experiments show that while the subdivision of cell cycle steps is conserved across a wide range of temperatures (5–35°C), the relative duration of individual steps varies with temperature. We find that the transition into prometaphase is delayed at lower temperatures relative to other cell cycle events, arguing that it has a different mechanism of regulation. Using an in vivo biosensor, we quantified the ratio of activities of the major mitotic kinase, Cdk1 and one of the major mitotic phosphatases PP1. Comparing activation profile with cell cycle transition times at different temperatures indicates that in early fly embryos activation of Cdk1 drives entry into prometaphase but is not required for earlier cell cycle events. In fact, chromosome condensation can still occur when Cdk1 activity is inhibited pharmacologically. These results demonstrate that different kinases are rate-limiting for different steps of mitosis, arguing that robust inter-regulation may be needed for rapid and ordered mitosis.
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