Fluctuations in Cyclin E levels are required for multiple rounds of endocycle S phase in Drosophila
Fluctuations in Cyclin E levels are required for multiple rounds of endocycle S phase in Drosophila
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DOI：
10.1016/s0960-9822(98)70089-2
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发表时间：
1998-02-12
期刊：
影响因子：
9.2
通讯作者：
O'Farrell, PH
中科院分区：
文献类型：
--
作者：
Follette, PJ;Duronio, RJ;O'Farrell, PH
细胞周期S期和有丝分裂的精确交替是由细胞核对S期诱导因子的交替反应能力控制的[1]，细胞核在细胞周期蛋白依赖性激酶（Cdk）活性的低点获得复制能力，该低点是细胞周期蛋白的有丝分裂破坏之后，在G1后期Cdk活性的升高被认为驱使细胞进入S期并阻止复制的DNA重新获得复制能力[2]。尽管在另一个复制周期之前通常需要有丝分裂来消除细胞周期蛋白，但在G2中实验性消除Cdk活性可以恢复复制能力[3-6]。在这里，我们研究了Cdks在果蝇内循环中的作用[7]。在这些周期中，没有中间有丝分裂的离散S期轮导致多线性。细胞周期蛋白A和B在进入内循环时在细胞中丢失[8，9]，并且细胞周期蛋白E表达的脉冲驱动内循环S期[10-12]。为了探讨Cyclin E表达的振荡是否是内循环所必需的，我们在果蝇唾液腺中连续表达Cyclin E，细胞的生长受到严重抑制，并诱导了一段时间的DNA复制，但进一步的复制受到抑制，这种复制抑制可以被激酶抑制剂6-DMAP克服，但不能被转录因子E2 F亚基的表达所克服。这些结果表明，内循环S阶段需要振荡的Cdk活性，但是，在有丝分裂细胞中的振荡相反，这些发生独立的有丝分裂。(C)当前生物有限公司
The precise cell-cycle alternation of S phase and mitosis is controlled by alternating competence of nuclei to respond to S-phase-inducing factors [1], Nuclei acquire competence to replicate at the low point in cyclin-dependent kinase (Cdk) activities that follows mitotic destruction of cyclins, The elevation of Cdk activity late in G1 is thought to drive cells into S phase and to block replicated DNA from re-acquiring replication competence [2]. Whereas mitosis is normally required to eliminate the cyclins prior to another cycle of replication, experimental elimination of Cdk activity in G2 can restore competence to replicate [3-6]. Here, we examine the roles of Cdks in the endocycles of Drosophila [7]. In these cycles, rounds of discrete S phases without intervening mitoses result in polyteny. Cyclins A and B are lost in cells as they enter endocycles [8,9], and pulses of Cyclin E expression drive endocycle S phases [10-12]. To address whether oscillations of Cyclin E expression are required for endocycles, we expressed Cyclin E continuously in Drosophila salivary glands, Growth of the cells was severely inhibited, and a period of DNA replication was induced but further replication was inhibited, This replication inhibition could be overcome by the kinase inhibitor 6-dimethylaminopurine (6-DMAP), but not by expression of subunits of the transcription factor E2F. These results indicate that endocycle S phases require oscillations in Cdk activity, but, in contrast to oscillations in mitotic cells, these occur independently of mitosis. (C) Current Biology Ltd.