Oxidative DNA damage through long-range electron transfer
Oxidative DNA damage through long-range electron transfer
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DOI：
10.1038/382731a0
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发表时间：
1996-08-22
期刊：
影响因子：
64.8
通讯作者：
Barton, JK
中科院分区：
文献类型：
--
作者：
Hall, DB;Holmlin, RE;Barton, JK
近四十年来，人们一直在考虑这样的可能性：DNA双螺旋包含杂环碱基对的π堆叠阵列，可能是电荷在长分子距离上迁移的合适介质（1-11）。这种高电荷迁移率的概念是关于DNA损伤的关键考虑因素。我们之前已经发现（7-10）DNA双螺旋可以作为金属嵌入剂之间光诱导电子转移的分子桥梁，速率快（大于或等于10（10）s（-1））（10）并且在很长一段时间内猝灭（>40埃）（8）。在这里，我们使用一种金属嵌入剂，将一个光激发的空穴引入到DNA的π-堆叠在一个特定的网站，以评估氧化损伤的DNA从一个距离。制备寡聚DNA双链体，其中铑嵌入剂共价连接到一端，并在空间上与5 '-GG-3'氧化双联体位点分离。铑诱导的光氧化特别发生在5 '-GG-3'双峰中的5 '-G处，并且在远离铑嵌入位点高达37埃处观察到。我们发现，氧化损伤的产量依赖于敏感的氧化电位和π堆积，但不是距离。这些结果直接表明，对DNA的氧化损伤可以从远程位点促进，作为空穴迁移通过DNA π堆叠的结果。
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(1-11). This notion of high charge mobility is a critical consideration with respect to DNA damage. We have previously found(7-10) that the DNA double helix can serve as a molecular bridge for photo-induced electron transfer between metallointercalators, with fast rates (greater than or equal to 10(10) s(-1))(10) and with quenching over a long distance (>40 Angstrom)(8). Here we use a metallointercalator to introduce a photoexcited hole into the DNA pi-stacked 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 Angstrom 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.