Oxoguanine glycosylase

8-Oxoguanine glycosylase also known as OGG1 is a is_associated_with::DNA glycosylase enzyme that, in humans, is encoded by the OGG1 is_associated_with::gene. It is involved in is_associated_with::base excision repair. It is found in is_associated_with::bacterial, is_associated_with::archaeal and is_associated_with::eukaryotic is_associated_with::species.

Function
OGG1 is the primary enzyme responsible for the excision of is_associated_with::8-oxoguanine (8-oxoG), a mutagenic base byproduct that occurs as a result of exposure to is_associated_with::reactive oxygen species (ROS). OGG1 is a bifunctional glycosylase, as it is able to both cleave the glycosidic bond of the mutagenic lesion and cause a strand break in the DNA backbone. Alternative splicing of the C-terminal region of this gene classifies splice variants into two major groups, type 1 and type 2, depending on the last exon of the sequence. Type 1 alternative splice variants end with exon 7 and type 2 end with exon 8. All variants have the N-terminal region in common. Many alternative splice variants for this gene have been described, but the full-length nature for every variant has not been determined. In eukaryotes, the N-terminus of this gene contains a mitochondrial targeting signal, essential for mitochondrial localization. A conserved N-terminal domain contributes residues to the 8-oxoguanine binding pocket. This domain is organised into a single copy of a TBP-like fold.

Despite the presumed importance of this enzyme, mice lacking Ogg1 have been generated and found to have a normal lifespan, and Ogg1 knockout mice have a higher probability to develop cancer, whereas Mth1 gene disruption concomitantly suppresses lung cancer development in Ogg1-/- mice. Interestingly, mice lacking Ogg1 have been shown to be prone to increased body weight and obesity, as well as high-fat diet induced insulin resistance. There is some controversy as to whether deletion of Ogg1 actually leads to increased 8-oxo-dG levels: the HPLC-EC assay suggests up to 6 fold higher levels of 8-oxo-dG in nuclear DNA and 20-fold higher in mitochondrial DNA whereas the fappy-glycosylase assay indicates no change.

Interactions
Oxoguanine glycosylase has been shown to interact with is_associated_with::XRCC1 and is_associated_with::PKC alpha.

Pathology

 * OGG1 may be associated with cancer risk in is_associated_with::BRCA1 and is_associated_with::BRCA2 mutation carriers.