Long-range and short-range oxidative damage to DNA: Photoinduced damage to guanines in ethidium-DNA assemblies
Long-range and short-range oxidative damage to DNA: Photoinduced damage to guanines in ethidium-DNA assemblies
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DOI：
10.1021/bi981750c
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发表时间：
1998-11-10
期刊：
影响因子：
2.9
通讯作者：
Barton, JK
中科院分区：
文献类型：
--
作者：
Hall, DB;Kelley, SO;Barton, JK
乙锭和DNA之间的短程和长程光反应已经被表征。虽然在激发到乙锭的可见吸收带时没有观察到DNA反应，但更高能量的照射（313-340 nm）导致在5 '-GG-3'双联体的5 '-G处的直接链切割和在鸟嘌呤处的哌啶敏感性损伤。这种反应性是不一致的鸟嘌呤的氧化通过电子转移或单线态氧所示的铑嵌入剂和亚甲蓝的反应，分别比较。通过将乙锭共价连接到DNA双链体的一端，我们证明了存在两种不同的反应，一种是短程反应，另一种是长程反应。短程反应涉及通过乙锭共价修饰鸟嘌呤，基于对核苷产物的HPLC分析和对乙锭衍生物的研究。长程反应与DNA介导的电子转移对鸟嘌呤的氧化反应完全一致。这种电子转移反应的产率不随距离而衰减;在近端（17埃Et-GG分离）和远端（44埃Et-GG分离）位点观察到相等的鸟嘌呤损伤产率。这些结果是非常相似的那些先前观察到的共价束缚铑光氧化剂和强调的独特能力的DNA碱基堆，以促进远程电子转移，从而影响氧化损伤的距离。
Short-range and long-range photoreactions between ethidium and DNA have been characterized. While no DNA reaction is observed upon excitation into the visible absorption band of ethidium, higher-energy irradiation (313-340 nm) leads both to direct strand cleavage at the 5'-G of 5'-GG-3' doublets and to piperidine-sensitive lesions at guanine. This reactivity is not consistent with oxidation of guanine by either electron transfer or singlet oxygen as shown by comparison with reactions of a rhodium intercalator and methylene blue, respectively. By covalently tethering ethidium to one end of a DNA duplex, we demonstrate the presence of two distinct reactions, one short-range and the other long-range. The short-range reaction involves a covalent modification of guanine by ethidium, based upon HPLC analysis of the nucleoside products and studies with ethidium derivatives. The long-range reaction is entirely consistent with oxidation of guanine by DNA-mediated electron transfer. The yield of this electron-transfer reaction is not attenuated with distance; equal yields of guanine damage are observed at a proximal (17 Angstrom Et-GG separation) and distal (44 Angstrom Et-GG separation) site. These results are quite similar to those previously observed with a covalently tethered rhodium photooxidant and underscore the unique ability of the DNA base stack to facilitate long-range electron transfer so as to effect oxidative damage from a distance.