8-oxoguanine DNA glycosylase 1 (OGG1) (OGG1)

8-oxoguanine DNA glycosylase 1 (OGG1) is a primary enzyme in the base excision repair (BER) pathway, specifically responsible for the recognition and excision of 8-oxoguanine (8-oxoG), a major mutagenic DNA lesion caused by reactive oxygen species (UniProt; PubMed). Beyond its canonical role in maintaining genomic stability, OGG1 acts as a redox-sensitive modulator and a pioneer factor that regulates the transcription of pro-inflammatory and pro-fibrotic genes by binding to 8-oxoG in promoter regions (PubMed; PMC). In cancer, OGG1 is often upregulated, and its inhibition can sensitize tumor cells to DNA-damaging agents or exploit synthetic lethality in repair-deficient backgrounds (ACS Publications; NIST). Conversely, OGG1 inhibitors show promise in treating chronic inflammatory conditions like asthma and COPD by dampening the expression of inflammatory mediators (Signal Transduction and Targeted Therapy). The enzyme's dual functionality as both a repair protein and a signaling molecule makes it a unique target for modulating cellular responses to oxidative stress (MDPI). While small-molecule inhibitors like TH5487 are in preclinical development, challenges include potential off-target effects on cellular efflux pumps and the need to selectively target pathological signaling without compromising global DNA integrity (PMC; BOC Sciences).

Other names

8-oxoguanine DNA glycosylaseN-glycosylase/DNA lyase8-hydroxyguanine DNA glycosylasehOGG1

Inhibition of DNA glycosylase activity and Schiff base formation, blocking the recognition and excision of 8-oxoguanine lesions, and suppressing OGG1-mediated pro-inflammatory transcriptional signaling (ACS Publications; BOC Sciences).