Genome-Wide Mapping of Oxidative DNA Damage via Engineering of 8‑Oxoguanine DNA Glycosylase

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.