Genome-Wide Mapping of Oxidative DNA Damage via Engineering of 8-Oxoguanine DNA Glycosylase
Genome-Wide Mapping of Oxidative DNA Damage via Engineering of 8-Oxoguanine DNA Glycosylase
复制标题
DOI：
10.1021/acs.biochem.9b00782
复制
发表时间：
2020-01-14
期刊：
影响因子：
2.9
通讯作者：
Zou, Peng
中科院分区：
文献类型：
--
作者：
Fang, Yuxin;Zou, Peng
8-氧代-7，8-二氢鸟嘌呤（OG）作为DNA氧化损伤的一种，参与了从基因突变到转录调控等一系列生物学过程。全基因组范围内的氧化损伤图谱可以揭示潜在的细胞机制。在本研究中，我们将hOGG 1酶（一种主要的8-氧代鸟嘌呤DNA糖基化酶）改造成鸟嘌呤氧化分析工具。我们的方法，称为enTRAP-seq，成功地确定了小鼠胚胎成纤维细胞基因组中超过1400个鸟嘌呤氧化位点。这些OG峰富集在开放的染色质区域和调控元件中，包括启动子、5'非翻译区和CpG岛。总的来说，我们提出了一个简单的和可推广的方法，具有高灵敏度和特异性的DNA损伤的全基因组分析。
The occurrence of 8-oxo-7,8-dihydroguanine (OG) in the genome, as one of the major DNA oxidative damages, has been implicated in an array of biological processes, ranging from mutagenesis to transcriptional regulation. Genome-wide mapping of oxidative damages could shed light on the underlying cellular mechanism. In the present study, we engineered the hOGG1 enzyme, a primary 8-oxoguanine DNA glycosylase, into a guanine oxidation-profiling tool. Our method, called enTRAP-seq, successfully identified more than 1400 guanine oxidation sites in the mouse embryonic fibroblast genome. These OG peaks were enriched in open chromatin regions and regulatory elements, including promoters, 5' untranslated regions, and CpG islands. Collectively, we present a simple and generalizable approach for the genome-wide profiling of DNA damages with high sensitivity and specificity.