A Matter of Life or Death: Modeling DNA Damage and Repair in Bacteria
A Matter of Life or Death: Modeling DNA Damage and Repair in Bacteria
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DOI：
10.1016/j.bpj.2010.12.3713
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发表时间：
2011-02-16
影响因子：
3.4
通讯作者：
de Moura, Alessandro P. S.
中科院分区：
文献类型：
--
作者：
Karschau, Jens;de Almeida, Camila;de Moura, Alessandro P. S.
DNA损伤是所有细胞都必须面对的危险，进化创造了许多修复染色体中受损碱基的机制。奇怪的是，许多这些修复机制可以在DNA分子中产生双链断裂，这对细胞是致命的。这表明DNA修复和死亡之间的联系远非简单明了，并表明修复机制可能是一把双刃剑。在这份报告中，我们制定了一个数学模型的DNA损伤和修复的动力学，我们得到的死亡率的解析表达式。我们预测生存和修复之间存在一种违反直觉的关系。我们可以区分两个阶段：低于修复酶数量的临界阈值，半衰期随修复酶数量的增加而减少，但与阈值以上的修复酶数量无关。我们能够定量地预测死亡率对损伤率和其他相关参数的依赖关系。我们通过模拟DNA损伤和修复的随机动力学来验证我们的分析结果。最后，我们还用大肠杆菌细胞进行了一个实验，以测试我们的模型的预测之一。
DNA damage is a hazard all cells must face, and evolution has created a number of mechanisms to repair damaged bases in the chromosome. Paradoxically, many of these repair mechanisms can create double-strand breaks in the DNA molecule which are fatal to the cell. This indicates that the connection between DNA repair and death is far from straightforward, and suggests that the repair mechanisms can be a double-edged sword. In this report, we formulate a mathematical model of the dynamics of DNA damage and repair, and we obtain analytical expressions for the death rate. We predict a counterintuitive relationship between survival and repair. We can discriminate between two phases: below a critical threshold in the number of repair enzymes, the half-life decreases with the number of repair enzymes, but becomes independent of the number of repair enzymes above the threshold. We are able to predict quantitatively the dependence of the death rate on the damage rate and other relevant parameters. We verify our analytical results by simulating the stochastic dynamics of DNA damage and repair. Finally, we also perform an experiment with Escherichia coli cells to test one of the predictions of our model.