Universal temporal profile of replication origin activation in eukaryotes.
Universal temporal profile of replication origin activation in eukaryotes.
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DOI：
10.1371/journal.pone.0005899
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发表时间：
2009-06-12
期刊：
影响因子：
3.7
通讯作者：
Hyrien O
中科院分区：
文献类型：
--
作者：
Goldar A;Marsolier-Kergoat MC;Hyrien O
虽然复制蛋白在真核生物中是保守的，但复制起始的序列要求在物种之间是不同的。然而，在所有物种中，复制起点在整个S阶段都是异步启动的。起源放电的时间程序在细胞群体中是可重现的，但在单细胞水平上很大程度上是概率的。这一计划的机制和意义尚不清楚。在后生动物中，复制时间与基因活性相关，而在酵母中则不相关。对起始激发进行时间调节的一个潜在作用是最小化复制结束时间的波动，避免未复制的DNA在有丝分裂中持续存在。在这里，我们从全基因组复制计时和DNA梳理数据中提取了酿酒酵母、庞氏葡萄球菌、黑腹葡萄球菌、莱维氏X.laevis和智人的复制起始率的种群平均时间分布。各剖面形态极为相似，在S期前半期呈上升趋势，末期呈下降趋势。以前提出的一个最小随机启动模型，通过积累一个可循环的、有限的复制分叉因子和分叉促进的新起始点的启动，定量地描述了观察到的轮廓，而不需要新的实现。及时完成基因组复制的选择性压力和必须输入到细胞核中的复制蛋白的最佳使用可以解释图谱的一般形状。我们已经确定了真核生物复制启动的普遍行为，它超越了起源规范的机制。在一组高度多样化的真核生物中，S阶段复制起点使用的群体平均效率以惊人的相似方式发生变化。先前提出的莱氏X.laevis起源激活的定量模型可以推广到解释这种进化守恒。
Although replication proteins are conserved among eukaryotes, the sequence requirements for replication initiation differ between species. In all species, however, replication origins fire asynchronously throughout S phase. The temporal program of origin firing is reproducible in cell populations but largely probabilistic at the single-cell level. The mechanisms and the significance of this program are unclear. Replication timing has been correlated with gene activity in metazoans but not in yeast. One potential role for a temporal regulation of origin firing is to minimize fluctuations in replication end time and avoid persistence of unreplicated DNA in mitosis. Here, we have extracted the population-averaged temporal profiles of replication initiation rates for S. cerevisiae, S. pombe, D. melanogaster, X. laevis and H. sapiens from genome-wide replication timing and DNA combing data. All the profiles have a strikingly similar shape, increasing during the first half of S phase then decreasing before its end. A previously proposed minimal model of stochastic initiation modulated by accumulation of a recyclable, limiting replication-fork factor and fork-promoted initiation of new origins, quantitatively described the observed profiles without requiring new implementations. The selective pressure for timely completion of genome replication and optimal usage of replication proteins that must be imported into the cell nucleus can explain the generic shape of the profiles. We have identified a universal behavior of eukaryotic replication initiation that transcends the mechanisms of origin specification. The population-averaged efficiency of replication origin usage changes during S phase in a strikingly similar manner in a highly diverse set of eukaryotes. The quantitative model previously proposed for origin activation in X. laevis can be generalized to explain this evolutionary conservation.
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影响因子：
3.7
作者：
Goldar, Arach;Labit, Helene;Hyrien, Olivier
通讯作者：
Hyrien, Olivier
影响因子：
14.9
作者：
Labit, Helene;Perewoska, Irene;Marheineke, Kathrin
通讯作者：
Marheineke, Kathrin
影响因子：
5.6
作者：
Czajkowsky, Daniel M.;Liu, Jie;Shao, Zhifeng
通讯作者：
Shao, Zhifeng
影响因子：
5.3
作者：
Nougarède, R;Della Seta, F;Schwob, E
通讯作者：
Schwob, E
影响因子：
11.4
作者：
HYRIEN, O;MECHALI, M
通讯作者：
MECHALI, M