Deciphering DNA replication dynamics in eukaryotic cell populations in relation with their averaged chromatin conformations.
Deciphering DNA replication dynamics in eukaryotic cell populations in relation with their averaged chromatin conformations.
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DOI：
10.1038/srep22469
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发表时间：
2016-03-03
影响因子：
4.6
通讯作者：
Hyrien O
中科院分区：
文献类型：
--
作者：
Goldar A;Arneodo A;Audit B;Argoul F;Rappailles A;Guilbaud G;Petryk N;Kahli M;Hyrien O
我们提出了一种 DNA 复制的非局部模型，该模型考虑了在真核细胞群中观察到的复制起始位置和时间的不确定性。通过将复制起始描绘为两种状态系统并考虑所有可能的转变配置，并考虑染色质的分形维数，我们推导出复制起始速率的分析表达式。该模型在没有自由参数的情况下预测起始速率、复制叉密度和复制 DNA 分数的时间分布，与来自酿酒酵母和人类细胞的相应实验数据定量一致，并提供起始位点冗余的定量估计。这项研究表明，在很大程度上，调节真核DNA复制动态的程序是一种集体现象，源于复制起点起始的随机性。
We propose a non-local model of DNA replication that takes into account the observed uncertainty on the position and time of replication initiation in eukaryote cell populations. By picturing replication initiation as a two-state system and considering all possible transition configurations, and by taking into account the chromatin’s fractal dimension, we derive an analytical expression for the rate of replication initiation. This model predicts with no free parameter the temporal profiles of initiation rate, replication fork density and fraction of replicated DNA, in quantitative agreement with corresponding experimental data from both S. cerevisiae and human cells and provides a quantitative estimate of initiation site redundancy. This study shows that, to a large extent, the program that regulates the dynamics of eukaryotic DNA replication is a collective phenomenon that emerges from the stochastic nature of replication origins initiation.