Department of Botany III, Unigruppe at the Max-Planck-Institute for Plant Breeding Research, Max-Delbrück-Laboratorium, University of Cologne, 50829 Cologne, Germany.
Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15275-80. doi: 10.1073/pnas.1006941107. Epub 2010 Aug 9.
One of the predominant cell-cycle programs found in mature tissues is endoreplication, also known as endoreduplication, that leads to cellular polyploidy. A key question for the understanding of endoreplication cycles is how oscillating levels of cyclin-dependent kinase activity are generated that control repeated rounds of DNA replication. The APC/C performs a pivotal function in the mitotic cell cycle by promoting anaphase and paving the road for a new round of DNA replication. However, using marker lines and plants in which APC/C components are knocked down, we show here that outgrowing and endoreplicating Arabidopsis leaf hairs display no or very little APC/C activity. Instead we find that RBX1-containing Cullin-RING E3 ubiquitin-Ligases (CRLs) are of central importance for the progression through endoreplication cycles; in particular, we have identified CULLIN4 as a major regulator of endoreplication in Arabidopsis trichomes. We have incorporated our findings into a bio-mathematical simulation presenting a robust two-step model of endoreplication control with one type of cyclin-dependent kinase inhibitor function for entry and a CRL-dependent oscillation of cyclin-dependent kinase activity via degradation of a second type of CDK inhibitor during endoreplication cycles.
在成熟组织中发现的主要细胞周期程序之一是内复制，也称为内复制，它导致细胞多倍体。理解内复制周期的一个关键问题是如何产生振荡的细胞周期蛋白依赖性激酶活性水平，从而控制重复的 DNA 复制。APC/C 通过促进后期和为新一轮 DNA 复制铺平道路，在有丝分裂细胞周期中发挥着关键作用。然而，使用标记线和 APC/C 成分被敲除的植物，我们在这里表明，正在生长和进行内复制的拟南芥叶毛显示出 APC/C 活性很低或没有。相反，我们发现含有 RBX1 的 Cullin-RING E3 泛素连接酶 (CRLs) 对通过内复制循环的进展至关重要；特别是，我们已经确定 CULLIN4 是拟南芥毛状体内复制的主要调节剂。我们将研究结果纳入生物数学模拟中，提出了一个稳健的两步内复制控制模型，其中一种细胞周期蛋白依赖性激酶抑制剂功能用于进入，并且通过在内复制循环期间降解第二种 CDK 抑制剂来进行 CRL 依赖性细胞周期蛋白依赖性激酶活性的振荡。
