由DNA修复酶的氧化还原反应介导的加速搜索动力学
Accelerated search kinetics mediated by redox reactions of DNA repair enzymes
摘要：
在几篇论文中已经提出了电荷传输（CT）机制（例如，Yavin等人，PNAS，v102 3546（2005））来解释碱基切除修复（BER）酶对DNA上的损伤的定位。CT机制依赖于铁-硫辅因子的氧化还原反应，其改变酶的结合亲和力。这些氧化还原反应由DNA链介导，并涉及BER酶之间沿DNA的电子交换。我们提出了一个数学模型，结合酶结合/解结合，电子传递，和酶沿DNA扩散。在一系列参数值范围内对我们的模型进行的分析表明，氧化还原反应可以增加BER酶的解吸附，使酶能够回收利用，从而加速整个搜索过程。当酶的拷贝数和沿着DNA的酶扩散率很小时，这种加速机制是最有效的。在这样的条件下，我们发现CT BER酶比简单的“被动”酶更快地找到它们的靶点，简单的“被动”酶只是附着在DNA上而不解吸。
英文摘要：
A Charge Transport (CT) mechanism has been proposed in several papers (e.g., Yavin, et al. PNAS, v102 3546 (2005)) to explain the localization of Base Excision Repair (BER) enzymes to lesions on DNA. The CT mechanism relies on redox reactions of iron-sulfur cofactors that modify the enzyme's binding affinity. These redox reactions are mediated by the DNA strand and involve the exchange of electrons between BER enzymes along DNA. We propose a mathematical model that incorporates enzyme binding/unbinding, electron transport, and enzyme diffusion along DNA. Analysis of our model within a range of parameter values suggests that the redox reactions can increase desorption of BER enzymes not already bound to their targets, allowing the enzymes to be recycled, thus accelerating the overall search process. This acceleration mechanism is most effective when enzyme copy numbers and enzyme diffusivity along the DNA are small. Under such conditions, we find that CT BER enzymes find their targets more quickly than simple "passive" enzymes that simply attach to the DNA without desorbing.
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