Effects of the stimuli-dependent enrichment of 8-oxoguanine DNA glycosylase1 on chromatinized DNA

The repair protein 8-oxoguanine DNA glycosylase 1 (OGG1) modulates gene expression upon its stimulus-driven binding to gene regulatory regions. ROS generated by receptor ligand interactions, metabolic processes, or environmental exposures produces 8-oxoguanine (8-oxoG) primarily in guanine-rich gene regulatory regions and inactivates OGG1's enzymatic activity by oxidizing it at cysteine residue(s) (OGG1-SOH). OGG1-SOH flips 8-oxoG out of the DNA double helix and induces alterations in adjacent DNA sequences, by which it facilitates binding of transcription factors. This leads to expression of genes and downstream cellular biological responses. Upon the cellular redox is reestablished, genomic 8-oxoG is repaired via the BER pathway. OGG1-SH, enzymatically active OGG1; OGG1-SOH, enzyatically inactive OGG1; BER, base excision repair; red star: 8-oxoguanine; red bar: gene regulatory region; blue bars: exons.210