Núñez M E, Holmquist G P, Barton J K
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Biochemistry. 2001 Oct 23;40(42):12465-71. doi: 10.1021/bi011560t.
Oxidative damage to DNA bases in isolated HeLa nuclei occurs upon treatment with rhodium intercalators and photoactivation. Oxidation occurs preferentially at the 5'-guanine of 5'-GG-3' sites, indicative of base damage by DNA-mediated charge transfer chemistry. Moreover, oxidative damage occurs at protein-bound sites which are inaccessible to rhodium. Thus, on transcriptionally active DNA within the cell nucleus, DNA-mediated charge transport leads to base damage from a distance, and direct interaction of an oxidant is not necessary to generate a base lesion at a specific site. These observations require consideration in designing new chemotherapeutics and in understanding cellular mechanisms for DNA damage and repair.
用铑嵌入剂处理并进行光激活后，分离出的HeLa细胞核中的DNA碱基会发生氧化损伤。氧化优先发生在5'-GG-3'位点的5'-鸟嘌呤处，这表明DNA介导的电荷转移化学作用导致碱基损伤。此外，氧化损伤发生在铑无法进入的蛋白质结合位点。因此，在细胞核内转录活跃的DNA上，DNA介导的电荷传输会导致远距离的碱基损伤，并且在特定位点产生碱基损伤并不一定需要氧化剂的直接相互作用。在设计新的化疗药物以及理解DNA损伤和修复的细胞机制时，需要考虑这些观察结果。
