电荷转运介导的DNA修复酶的募集
Charge transport-mediated recruitment of DNA repair enzymes
摘要：
DNA中受损或错配的碱基可以通过碱基切除修复（BER）酶来修复，该酶替换有缺陷的碱基。虽然许多BER酶的详细分子结构是已知的，但它们如何共定位于病变仍不清楚。一种假设涉及沿着DNA的电荷传输（CT）[Yavin，{ \it et al.}，PNAS，{ \bf 102}，3546，（2005）]。在这种CT机制中，电子被最近吸附的BER酶释放并沿着DNA行进。电子可以散射（通过沿着DNA的异质性）回到酶，使其不稳定并将其从DNA上敲下，或者，它们可以被附近的病变和鸟嘌呤自由基吸收。我们建立了一个随机模型来描述电子动力学，并计算了鸟嘌呤自由基和修复酶捕获电子的概率。我们还计算了电子返回的第一次通过时间，并将这些结果在鸟嘌呤自由基分布上整体平均。我们的统计结果提供的规则，使我们能够进行隐式电子蒙特卡罗模拟修复酶的结合和再分布病变附近。当病变是电子吸收，我们表明，CT机制抑制浪费的积累酶沿完整的DNA部分，最大限度地提高酶浓度附近的病变。
英文摘要：
Damaged or mismatched bases in DNA can be repaired by Base Excision Repair (BER) enzymes that replace the defective base. Although the detailed molecular structures of many BER enzymes are known, how they colocalize to lesions remains unclear. One hypothesis involves charge transport (CT) along DNA [Yavin, {\it et al.}, PNAS, {\bf 102}, 3546, (2005)]. In this CT mechanism, electrons are released by recently adsorbed BER enzymes and travel along the DNA. The electrons can scatter (by heterogeneities along the DNA) back to the enzyme, destabilizing and knocking it off the DNA, or, they can be absorbed by nearby lesions and guanine radicals. We develop a stochastic model to describe the electron dynamics, and compute probabilities of electron capture by guanine radicals and repair enzymes. We also calculate first passage times of electron return, and ensemble-average these results over guanine radical distributions. Our statistical results provide the rules that enable us to perform implicit-electron Monte-Carlo simulations of repair enzyme binding and redistribution near lesions. When lesions are electron absorbing, we show that the CT mechanism suppresses wasteful buildup of enzymes along intact portions of the DNA, maximizing enzyme concentration near lesions.
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