8-Oxoguanine DNA glycosylase (OGG1)

8-Oxoguanine DNA glycosylase (OGG1) is a bifunctional DNA repair enzyme responsible for recognizing and excising 8-oxoguanine—a mutagenic oxidative lesion formed in DNA due to reactive oxygen species exposure—from both nuclear and mitochondrial DNA as the critical first step in the base excision repair pathway[6][7]. OGG1 cleaves the glycosidic bond to release the damaged base and then incises the DNA backbone via AP lyase activity, preventing G:C to T:A transversion mutations and maintaining genomic stability[4][3]. Beyond repair, OGG1 participates in transcriptional regulation and cellular signaling, including modulating the activity of Ras and Rac GTPases and the expression of immune and inflammatory genes[5][2]. Altered OGG1 expression or activity is implicated in various diseases, including cancer, inflammation, and neurodegenerative disorders, making it a candidate therapeutic target for drug discovery focused on modulating DNA repair or the cellular response to oxidative stress[1][6][9].

Other names

N-glycosylase/DNA lyaseDNA-(apurinic or apyrimidinic site) lyaseMMHMUTMOGH1AP lyaseHMMHHOGG18-hydroxyguanine DNA glycosylaseOGG1 type 1eOGG1 type 1dOGG1 type 1gOGG1 type 1hOGG1 type 1f

Inhibition of OGG1 leads to accumulation of 8-oxoguanine lesions, increasing DNA damage and mutation rate. Activation of OGG1 enhances base excision repair, potentially protective against oxidative stress. Modulation of OGG1 enzymatic or signaling functions (e.g., affecting its role in gene transcription or Ras pathway activation) is also a mechanism of action.