OGG1
OGG1 (8-oxoguanine DNA glycosylase 1) is the base-excision repair enzyme that removes 8-oxoguanine, the most abundant oxidative lesion in DNA, from the genome.
Function
Reactive oxygen species generated by mitochondria convert guanine to 8-oxoguanine, which pairs with adenine as readily as with cytosine; an unrepaired 8-oxoG therefore becomes a G→T transversion after one round of replication. OGG1 scans DNA, flips 8-oxoguanine out of the helix into its active site, cleaves the damaged base from the sugar, and transfers the resulting abasic site to the downstream base-excision repair enzymes (APE1, polymerase β, ligase) that restore the strand. The enzyme preferentially finds 8-oxoG in the transcribed strand of active genes, where transcription-coupled repair concentrates it.
In cancer
The G→T transversions that unrepaired 8-oxoG produces are a common mutational signature in p53 in lung tumors of smokers, where reactive oxidants from smoke raise the lesion load. OGG1 knockout mice accumulate 8-oxoG and show elevated mutation rates without a strong spontaneous cancer phenotype, indicating redundancy with other repair routes. OGG1 activity declines with age in some tissues, tying oxidative mutation supply to the aging genome.
Notes
- Human gene symbol: OGG1; UniProt O15527; 345 amino acids; helix-hairpin-helix glycosylase family.