DNA replication licensing affects cell proliferation or endoreplication in a cell type-specific manner
DNA replication licensing affects cell proliferation or endoreplication in a cell type-specific manner
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DOI：
10.1105/tpc.104.022400
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发表时间：
2004-09-01
期刊：
影响因子：
11.6
通讯作者：
Gutierrez, C
中科院分区：
文献类型：
--
作者：
Castellano, MD;Boniotti, MB;Gutierrez, C
在真核细胞中，DNA复制许可组件(CDC6和CDT1等)的功能对细胞增殖和基因组稳定性至关重要。然而，对于它们在整个生物体中的作用，以及许可控制是否与分化和发育计划相联系，人们知之甚少。在这里，我们研究了拟南芥CDT1，它的调控，以及凌驾于许可控制之上的后果。AtCDT1的可获得性在两个水平上受到严格的调控：(1)在转录水平上，受E2F和生长抑制信号的调控；(2)在转录后，受CDK磷酸化的调控，这是蛋白酶体介导的降解所必需的步骤。我们还表明CDC6和CDT1是协调细胞增殖、分化和发育的关键靶点。事实上，CDT1或CDC6水平的改变对拟南芥植物的发育具有细胞类型特异性的影响：在有能力分裂的叶细胞中，细胞增殖被刺激，而在被编程经历与分化相关的内复制轮的细胞中，额外的内环被触发。因此，我们认为，DNA复制许可控制对于适当维持增殖潜力、发育计划和形态发生模式至关重要。
In eukaryotic cells, the function of DNA replication licensing components (Cdc6 and Cdt1, among others) is crucial for cell proliferation and genome stability. However, little is known about their role in whole organisms and whether licensing control interfaces with differentiation and developmental programs. Here, we study Arabidopsis thaliana CDT1, its regulation, and the consequences of overriding licensing control. The availability of AtCDT1 is strictly regulated at two levels: (1) at the transcription level, by E2F and growth-arresting signals, and (2) posttranscriptionally, by CDK phosphorylation, a step that is required for its proteasome-mediated degradation. We also show that CDC6 and CDT1 are key targets for the coordination of cell proliferation, differentiation, and development. Indeed, altered CDT1 or CDC6 levels have cell type-specific effects in developing Arabidopsis plants: in leaf cells competent to divide, cell proliferation is stimulated, whereas in cells programmed to undergo differentiation-associated endoreplication rounds, extra endocycles are triggered. Thus, we propose that DNA replication licensing control is critical for the proper maintenance of proliferative potential, developmental programs, and morphogenetic patterns.