Hall D B, Holmlin R E, Barton J K
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125, USA.
Nature. 1996 Aug 22;382(6593):731-5. doi: 10.1038/382731a0.
The possibility has been considered for almost forty years that the DNA double helix, which contains a pi-stacked array of heterocyclic base pairs, could be a suitable medium for the migration of charge over long molecular distances. This notion of high charge mobility is a critical consideration with respect to DNA damage. We have previously found that the DNA double helix can serve as a molecular bridge for photo-induced electron transfer between metallointercalators, with fast rates (> or = 10(10)s-1) and with quenching over a long distance (>40 A). Here we use a metallointercalator to introduce a photoexcited hole into the DNA pi-stack at a specific site in order to evaluate oxidative damage to DNA from a distance. Oligomeric DNA duplexes were prepared with a rhodium intercalator covalently attached to one end and separated spatially from 5'-GG-3' doublet sites of oxidation. Rhodium-induced photo-oxidation occurs specifically at the 5'-G in the 5'-GG-3' doublets and is observed up to 37 A away from the site of rhodium intercalation. We find that the yield of oxidative damage depends sensitively upon oxidation potential and pi-stacking, but not on distance. These results demonstrate directly that oxidative damage to DNA may be promoted from a remote site as a result of hole migration through the DNA pi-stack.
近四十年来，人们一直在考虑这样一种可能性：包含π堆积杂环碱基对阵列的DNA双螺旋结构，可能是电荷在长分子距离上迁移的合适介质。这种高电荷迁移率的概念是DNA损伤方面的一个关键考虑因素。我们之前发现，DNA双螺旋结构可以作为金属嵌入剂之间光诱导电子转移的分子桥梁，转移速率很快（≥10¹⁰ s⁻¹），且能在长距离（>40 Å）上发生猝灭。在这里，我们使用一种金属嵌入剂在特定位置将光激发空穴引入DNA的π堆积中，以便从远处评估对DNA的氧化损伤。制备了寡聚DNA双链体，其一端共价连接有铑嵌入剂，并在空间上与氧化的5'-GG-3'双峰位点分开。铑诱导的光氧化作用特异性地发生在5'-GG-3'双峰中的5'-G处，并且在距离铑嵌入位点37 Å远的地方也能观察到。我们发现，氧化损伤的产率敏感地取决于氧化电位和π堆积，但与距离无关。这些结果直接表明，由于空穴通过DNA的π堆积迁移，DNA的氧化损伤可能会从远处的位点引发。
