Merino Edward J, Boal Amie K, Barton Jacqueline K
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, United States.
Curr Opin Chem Biol. 2008 Apr;12(2):229-37. doi: 10.1016/j.cbpa.2008.01.046. Epub 2008 Mar 17.
Many experiments have now shown that double helical DNA can serve as a conduit for efficient charge transport (CT) reactions over long distances in vitro. These results prompt the consideration of biological roles for DNA-mediated CT. DNA CT has been demonstrated to occur in biologically relevant environments such as within the mitochondria and nuclei of HeLa cells as well as in isolated nucleosomes. In mitochondria, DNA damage that results from CT is funneled to a crucial regulatory element. Thus, DNA CT provides a strategy to funnel damage to particular sites in the genome. DNA CT might also be important in long-range signaling to DNA-bound proteins. Both DNA repair proteins, containing Fe-S clusters, and the transcription factor, p53, which is regulated through thiol-disulfide switches, can be oxidized from a distance through DNA-mediated CT. These observations highlight a means through which oxidative stress may be chemically signaled in the genome over long distances through CT from guanine radicals to DNA-bound proteins. Moreover, DNA-mediated CT may also play a role in signaling among DNA-binding proteins, as has been proposed as a mechanism for how DNA repair glycosylases more efficiently detect lesions inside the cell.
现在许多实验表明，双螺旋DNA可作为体外长距离高效电荷转移（CT）反应的通道。这些结果促使人们考虑DNA介导的CT的生物学作用。已证明DNA CT发生在生物相关环境中，如在HeLa细胞的线粒体和细胞核内以及分离的核小体中。在线粒体中，由CT导致的DNA损伤会导向一个关键的调控元件。因此，DNA CT提供了一种将损伤导向基因组特定位点的策略。DNA CT在与DNA结合蛋白的长距离信号传导中可能也很重要。含有铁硫簇的DNA修复蛋白以及通过硫醇-二硫键开关调节的转录因子p53，都可以通过DNA介导的CT从远处被氧化。这些观察结果突出了一种方式，通过这种方式，氧化应激可以通过从鸟嘌呤自由基到与DNA结合蛋白的CT在基因组中进行长距离化学信号传导。此外，正如有人提出的DNA修复糖基化酶如何更有效地检测细胞内损伤的机制一样，DNA介导的CT也可能在与DNA结合蛋白之间的信号传导中发挥作用。
