8-Oxoguanine DNA Glycosylase (OGG1) (OGG1)

8-Oxoguanine DNA Glycosylase (OGG1) is the primary enzyme responsible for identifying and removing 8-oxoguanine (8-oxoG) lesions from DNA, which are caused by reactive oxygen species (UniProt: O00319). As a key component of the base excision repair (BER) pathway, OGG1 possesses both DNA glycosylase and AP lyase activities to initiate the repair of oxidative damage. Beyond DNA repair, OGG1 plays a significant role in cellular signaling; the complex formed between OGG1 and the excised 8-oxoG base can function as a guanine nucleotide exchange factor, activating Ras GTPases and promoting pro-inflammatory gene expression (PubMed: 30442760). In therapeutic development, OGG1 inhibitors like TH5487 are being investigated for their ability to suppress inflammation and treat various cancers by preventing the recruitment of transcription factors to damaged promoter regions (PubMed: 36379215). Conversely, enhancing OGG1 activity or utilizing mRNA-based delivery systems to increase OGG1 expression is a strategy aimed at protecting cells from age-related oxidative stress and neurodegeneration (PubMed: 35114100). Monitoring OGG1 mRNA and protein levels serves as a critical biomarker for assessing a cell's capacity to handle oxidative stress and its susceptibility to mutagenesis (PubMed: 29155424). The target is also relevant in the context of synthetic lethality, where OGG1 inhibition may selectively kill cancer cells with specific co-existing DNA repair deficiencies. Overall, OGG1 represents a versatile target for both inhibition in inflammatory and oncological contexts and activation in degenerative diseases.

Other names

8-Oxoguanine DNA Glycosylase 1AP lyaseDNA-oxoguanine glycosylaseMUTMOGH1hOGG1

Small molecule inhibition of the OGG1 enzyme prevents the repair of 8-oxoguanine lesions and blocks OGG1-mediated pro-inflammatory signaling pathways. Conversely, OGG1 activators or mRNA-based therapies aim to enhance the excision of oxidative DNA damage to maintain genomic integrity and reduce cellular senescence.