Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
J Am Chem Soc. 2010 Jan 27;132(3):891-905. doi: 10.1021/ja907669c.
The transport of charge through the DNA base-pair stack offers a route to carry out redox chemistry at a distance. Here we describe characteristics of this chemistry that have been elucidated and how this chemistry may be utilized within the cell. The shallow distance dependence associated with these redox reactions permits DNA-mediated signaling over long molecular distances in the genome and facilitates the activation of redox-sensitive transcription factors globally in response to oxidative stress. The long-range funneling of oxidative damage to sites of low oxidation potential in the genome also may provide a means of protection within the cell. Furthermore, the sensitivity of DNA charge transport to perturbations in base-pair stacking, as may arise with base lesions and mismatches, may be used as a route to scan the genome for damage as a first step in DNA repair. Thus, the ability of double-helical DNA in mediating redox chemistry at a distance provides a natural mechanism for redox sensing and signaling in the genome.
电荷通过 DNA 碱基对堆叠的传输为远距离进行氧化还原化学提供了一种途径。在这里，我们描述了已经阐明的这种化学的特征，以及这种化学在细胞内如何被利用。与这些氧化还原反应相关的浅距离依赖性允许 DNA 介导的信号在基因组中的长分子距离上传递，并促进氧化应激下全局的氧化还原敏感转录因子的激活。氧化损伤向基因组中氧化还原电势较低的部位的长程漏斗效应也可能为细胞内提供一种保护手段。此外，碱基对堆叠的扰动可能会影响 DNA 电荷传输的敏感性，就像碱基损伤和错配一样，因此可以将其作为扫描基因组中损伤的一种途径，作为 DNA 修复的第一步。因此，双链 DNA 在远距离介导氧化还原化学的能力为基因组中的氧化还原感应和信号提供了一种自然机制。
