OGG1 is a base excision repair enzyme that initiates DNA damage response by recognizing and excising 8-oxoguanine (8-oxoG), a common oxidative DNA lesion 1. The enzyme flips the damaged base out of the DNA duplex into its catalytic pocket and cleaves the glycosidic bond, leaving a substrate for downstream repair factors like APE1 2. OGG1 demonstrates context-dependent activity: it efficiently repairs 8-oxoG in linear DNA and at nucleosomal entry/exit sites, but encounters reduced efficiency when lesions are buried within nucleosomal internal positions due to histone occlusion 34. Beyond its canonical repair function, OGG1 acts as an epigenetic reader, as 8-oxoG accumulates preferentially in regulatory regions and OGG1-mediated recognition can modulate gene expression through DNA conformation changes 1. Clinically, OGG1 dysfunction associates with increased disease risk. Occupational arsenic exposure downregulates OGG1 expression, correlating with elevated DNA damage 5, while OGG1 polymorphisms modulate individual susceptibility to oxidative DNA damage from polyaromatic hydrocarbon exposure 6. At telomeres, OGG1-initiated repair generates single-stranded break intermediates that paradoxically trigger senescence, revealing repair completion is critical for genomic stability 7. Small-molecule OGG1 activators enhance repair capacity and may have therapeutic potential in aging and disease prevention 2.