Oxoguanine glycosylase
Encyclopedia
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
.
(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. The N-terminus of this gene contains a mitochondrial targeting signal, essential for mitochondrial localization.
Despite the presumed importance of this enzyme, mice lacking Ogg1 have been generated and found to have a normal lifespan, and despite some early reports, do not show increased mutagenesis or cancer incidence. 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.
with XRCC1
and PKC alpha
.
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. It is involved in base excision repair
Base excision repair
In biochemistry and genetics, base excision repair is a cellular mechanism that repairs damaged DNA throughout the cell cycle. It is responsible primarily for removing small, non-helix-distorting base lesions from the genome. The related nucleotide excision repair pathway repairs bulky...
.
Function
OGG1 is the primary enzyme responsible for the excision of 7,8-dihydro-8-oxoguanine8-oxoguanine
8-Oxoguanine is one of the most common DNA lesions resulting from reactive oxygen species and can result in a mismatched pairing with Adenine resulting in G to T and C to A substitutions in the genome. In humans, it is primarily repaired by the DNA glycosylase OGG1...
(8-oxoG), a mutagenic base byproduct that occurs as a result of exposure to reactive oxygen species
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
(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. The N-terminus of this gene contains a mitochondrial targeting signal, essential for mitochondrial localization.
Despite the presumed importance of this enzyme, mice lacking Ogg1 have been generated and found to have a normal lifespan, and despite some early reports, do not show increased mutagenesis or cancer incidence. 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 interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with XRCC1
XRCC1
XRCC1 is a DNA repair protein.It complexes with DNA ligase III.-Interactions:XRCC1 has been shown to interact with PARP2, DNA polymerase beta, Aprataxin, Oxoguanine glycosylase, PCNA, APEX1, PNKP and PARP1.-Further reading:-External links:...
and PKC alpha
PKC alpha
Protein kinase C alpha , also known as PRKCA, refers to both a human gene and the protein that is encoded by it.-Background:...
.