Isoform switching of Cdc6 contributes to developmental cell cycle remodeling.

Isoform switching of Cdc6 contributes to developmental cell cycle remodeling.
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Cdc6 的异构体转换有助于发育细胞周期重塑。

DOI:
10.1016/s0012-1606(03)00253-7
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发表时间:
2003
影响因子:
2.7
通讯作者:
Coleman,ThomasR
Coleman,ThomasR
中科院分区:
生物学3区
文献类型:
--
作者:
Tikhmyanova,Nadia;Coleman,ThomasR

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非洲爪蟾早期发育具有快速、同步的卵裂周期,由S期和M期交替组成。在中胚转变时,合子转录开始,这些卵裂周期被包括间隙期和检查点的更长的细胞分裂周期所取代。在此,我们证明了发育调节Cdc 6亚型转换,有助于这种发育细胞周期重塑。Cdc 6是真核生物DNA复制机器的重要组成部分,它在每个细胞分裂周期允许每个起点进行一轮DNA复制。最初的特点爪蟾Cdc 6同种型(这里称为Xcdc 6A)和一种新的同种型(Xcdc 6 B)有分歧的N-末端调控区和不同的时间模式的表达。虽然丰富的早期胚胎,Xcdc 6A变得无法检测到后中囊胚过渡。相反,虽然Xcdc 6 B存在于早期胚胎中,但它是无功能的,因为缺乏染色质结合。然而,在体细胞组织中,Xcdc 6 B结合染色质,其抑制阻断进入S期。这是Cdc 6发育调控的第一个例子,对胚胎发生过程中的细胞周期重塑产生了有趣的影响。
Xenopus laevis early development is characterized by rapid and synchronous cleavage cycles, which consist of alternating S and M phases. At midblastula transition, zygotic transcription begins and these cleavage cycles are replaced by longer cell division cycles that include gap phases and checkpoints. Herein, we demonstrate developmentally regulated Cdc6 isoform switching that contributes to this developmental cell cycle remodeling. Cdc6 is an essential component of the eukaryotic DNA replication machine that licenses each origin to one round of DNA replication each cell division cycle. The originally characterized Xenopus Cdc6 isoform (here termed Xcdc6A) and a novel isoform (Xcdc6B) have divergent N-terminal regulatory regions and different temporal patterns of expression. Although abundant in the early embryo, Xcdc6A becomes undetectable following midblastula transition. In contrast, while Xcdc6B is present in the early embryo, it is nonfunctional, as judged by lack of chromatin binding. In somatic tissue, however, Xcdc6B binds chromatin and its inhibition blocks entry into S phase. This is the first example of developmental regulation of Cdc6, raising intriguing implications for cell cycle remodeling during embryogenesis.
DOI: 10.1091/mbc.11.12.4117
发表时间: 2000-12-01
影响因子: 3.3
作者:
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