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Beschreibung

The protein named N-glycosylase/DNA lyase or alternatively, 8-oxoguanine (8-OxoG) DNA glycosylase or AP lyase, and encoded by the gene named OGG1/MMH/MUTM/OGH1, is a DNA repair enzyme that incises DNA at 8-oxoG residues and excises 7,8-dihydro-8-oxoguanine and 2,6-diamino-4-hydroy-5-N-methylformamidopyrimidine (FAPY) from damaged DNA. OGG1 also has beta-lyase activity that nicks DNA 3&prime, to the lesion. OGG1 is localized to the nucleus and nucleoplasm, in UVA-irradiated cells it can be found in the nuclear speckles. There is also an isoform found in the mitochondrion. Interestingly, OGG1 appears to be play a critical role in repairing mtDNA damage, mtDNA damage is linked to mitochondrial dysfunction, increased oxidative stress, and insulin resistance in muscle cells, and studies using OGG1 knockouts or over expressing OGG1 demonstrate that OGG1 is important for proper mtDNA damage repair and that disruption of OGG1 can lead to increased mtROS (reactive oxygen species) production and subsequent regulation of downstream events leading to insulin resistance in skeletal muscle. OGG1, or rather defects in OGG1 function, are also associated with a number of carcinomas, particularly Renal Cell Carcinomas of various cell types.