The Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, Jilin 130024, China; School of Life Science, Northeast Normal University, Changchun, Jilin 130024, China.
Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA; Sealy Center for Molecular Medicine, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
Redox Biol. 2018 Apr;14:669-678. doi: 10.1016/j.redox.2017.11.008. Epub 2017 Nov 10.
Oxidative stress and the resulting damage to genomic DNA are inevitable consequences of endogenous physiological processes, and they are amplified by cellular responses to environmental exposures. One of the most frequent reactions of reactive oxygen species with DNA is the oxidation of guanine to pre-mutagenic 8-oxo-7,8-dihydroguanine (8-oxoG). Despite the vulnerability of guanine to oxidation, vertebrate genes are primarily embedded in GC-rich genomic regions, and over 72% of the promoters of human genes belong to a class with a high GC content. In the promoter, 8-oxoG may serve as an epigenetic mark, and when complexed with the oxidatively inactivated repair enzyme 8-oxoguanine DNA glycosylase 1, provide a platform for the coordination of the initial steps of DNA repair and the assembly of the transcriptional machinery to launch the prompt and preferential expression of redox-regulated genes. Deviations/variations from this artful coordination may be the etiological links between guanine oxidation and various cellular pathologies and diseases during ageing processes.
氧化应激以及由此导致的基因组 DNA 损伤是内源性生理过程不可避免的后果，它们会被细胞对环境暴露的反应放大。活性氧与 DNA 最常见的反应之一是将鸟嘌呤氧化为前诱变的 8-氧代-7,8-二氢鸟嘌呤（8-oxoG）。尽管鸟嘌呤容易氧化，但脊椎动物基因主要嵌入 GC 丰富的基因组区域，超过 72%的人类基因启动子属于高 GC 含量的一类。在启动子中，8-oxoG 可以作为一种表观遗传标记，与氧化失活的修复酶 8-氧鸟嘌呤 DNA 糖基化酶 1 结合，为协调 DNA 修复的初始步骤和转录机制的组装提供平台，以启动氧化还原调节基因的快速和优先表达。这种巧妙协调的偏差/变化可能是在衰老过程中，鸟嘌呤氧化与各种细胞病理学和疾病之间的病因联系。
