Oxoguanine glycosylase

8-oxoguanine DNA glycosylase, N-terminal domain
File:PDB 2noh EBI.jpg structure of catalytically inactive q315a human 8-oxoguanine glycosylase complexed to 8-oxoguanine dna
Identifiers
Symbol	OGG_N
Pfam	PF07934
Pfam clan	CL0407
InterPro	IPR012904
SCOP	1ebm
SUPERFAMILY	1ebm
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

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

Function

OGG1 is the primary enzyme responsible for the excision of 8-oxoguanine (8-oxoG), a mutagenic base byproduct that occurs as a result of exposure to 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 XRCC1 and PKC alpha.

Pathology

• OGG1 may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers.

External links

• oxoguanine glycosylase 1, human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the public domain Pfam and InterPro IPR012904