8-Oxoguanine DNA glycosylase 1: Beyond repair of the oxidatively modified base lesions.
8-Oxoguanine DNA glycosylase 1: Beyond repair of the oxidatively modified base lesions.
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DOI：
10.1016/j.redox.2017.11.008
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发表时间：
2018-04
期刊：
影响因子：
11.4
通讯作者：
Boldogh I
中科院分区：
文献类型：
--
作者：
Ba X;Boldogh I
氧化应激和由此产生的基因组DNA损伤是内源性生理过程的必然结果，并且它们通过细胞对环境暴露的反应而放大。活性氧与DNA最常见的反应之一是鸟嘌呤氧化为预诱变的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在富含GC的基因组区域中，并且超过72%的人类基因的启动子属于具有高GC含量的类别。在启动子中，8-oxoG可以作为表观遗传标记，并且当与氧化失活的修复酶8-oxoguanine DNA糖基化酶1复合时，为DNA修复的初始步骤的协调和转录机器的组装提供平台，以启动氧化还原调节基因的迅速和优先表达。这种巧妙协调的偏差/变化可能是衰老过程中鸟嘌呤氧化与各种细胞病理和疾病之间的病因学联系。OGG 1与基因组8-氧代鸟嘌呤的结合促进基因表达。OGG 1对开放染色质区域的作用（左），OGG 1与其底物的结合促进转录因子（如NF-κB）的DNA占据并促进转录。如果鸟嘌呤氧化发生在封闭的染色质区域（右），OGG 1的结合可以阻断甲基结合蛋白（BMP）与其底物的相互作用，随后招募转录机器组件来激活转录。
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. Binding of OGG1 to genomic 8-oxoguanine facilitates gene expression. Proposed actions of OGG1 on open chromatin region (left), OGG1 binding to its substrate facilitates DNA occupancy of transcription factors (NF-κB is shown as example) and promote transcription. If guanine oxidation occurs at closed chromatin region (right), binding of OGG1 could block the interaction of methyl binding proteins (BMPs) with their substrates, subsequently recruit transcription machinery components to activate transcription.
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DOI：
10.4049/jimmunol.1401625
发表时间：
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期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
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发表时间：
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作者：
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影响因子：
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作者：
Bacsi, Attila;Aguilera-Aguirre, Leopoldo;Szczesny, Bartosz;Radak, Zsolt;Hazra, Tapas K.;Sur, Sanjiv;Ba, Xueqing;Boldogh, Istvan
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