8-oxoguanine (G*), induced by reactive oxygen species, is mutagenic because it mispairs with A. The major G*-DNA glycosylase (OGG), namely, OGG1 in eukaryotes, or MutM in Escherichia coli, excises G* when paired in DNA with C, G and T, but not A, presumably because removal of G* from a G* A pair would be mutagenic. However, repair of G* will prevent mutation when it is incorporated in the nascent strand opposite A. This could be carried out by a second OGG, OGG2, identified in yeast and human cells. We have now characterized a new OGG activity E. coli and then identified it to be endonuclease VIII (Nei) discovered as a damaged pyrimidine-specific DNA glycosylase. Nei shares sequence homology and reaction mechanism with MutM, and is similar to human OGG2 in being able to excise G* when paired with A (or G). Kinetic analysis of wild type Nei showed that it has significant activity for excising G* relative to Dihydrouracil. The presence of OGG2 type enzyme in both E. coli and Eukaryotes, which is at least as efficient in excision G* from a G* A(or G) pair as from a G* C pair, supports the possibility of G* repair in the nascent DNA strand.
Citation: Journal of Biological Chemistry
Issue: No. 36
Pub Type: Journals
DNA glycosylases, DNA repair, excision kinetics, mismatch repair, ogg2 protein, oxidative DNA damage