Blow J Julian, Ge Xin Quan
Wellcome Trust Centre for Gene Regulation & Expression, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
EMBO Rep. 2009 Apr;10(4):406-12. doi: 10.1038/embor.2009.5. Epub 2009 Feb 13.
Replication origins are 'licensed' for a single initiation event before entry into S phase; however, many licensed replication origins are not used, but instead remain dormant. The use of these dormant origins helps cells to survive replication stresses that block replication fork movement. Here, we present a computer model of the replication of a typical metazoan origin cluster in which origins are assigned a certain initiation probability per unit time and are then activated stochastically during S phase. The output of this model is in good agreement with experimental data and shows how inefficient dormant origins can be activated when replication forks are inhibited. The model also shows how dormant origins can allow replication to complete even if some forks stall irreversibly. This provides a simple explanation for how replication origin firing is regulated, which simultaneously provides protection against replicative stress while minimizing the cost of using large numbers of replication forks.
复制起点在进入S期之前会被“许可”进行单次起始事件；然而，许多被许可的复制起点并未被使用，而是处于休眠状态。这些休眠起点的启用有助于细胞在阻碍复制叉移动的复制应激中存活下来。在这里，我们展示了一个典型后生动物起源簇复制的计算机模型，其中起点被赋予每单位时间一定的起始概率，然后在S期随机激活。该模型的输出与实验数据高度吻合，并显示了在复制叉受到抑制时效率低下的休眠起点是如何被激活的。该模型还展示了即使一些复制叉不可逆地停滞，休眠起点如何使复制得以完成。这为复制起点激发的调控方式提供了一个简单的解释，它既能在最小化使用大量复制叉成本的同时提供针对复制应激的保护。
