Characterization of a novel 8-oxoguanine-DNA glycosylase activity in Escherichia coli and identification of the enzyme as endonuclease VIII

8-Oxoguanine (G*), induced by reactive oxygen species, is mutagenic because it mispairs with A. The major G*-DNA glycosylase (OGG), namely, OGG1 in eu karyotes, 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 wo uld be mutagenic. However, repair of G* will prevent mutation when it is in corporated in the nascent strand opposite A. This could be carried out by a second OGG, OGG2, identified in yeast and human cells. We have characteriz ed a new OGG activity in E, coli and then identified it to be endonuclease VIII (Nei), discovered as a damaged py. rimidine-specific DNA glycosylase, Nei shares sequence homology and reaction mechanism with MutM and is simila r to human OGG2 in being able to excise G* when paired with A (or G), Kinet ic analysis of wild type Nei showed that it has significant activity for ex cising G* relative to dihydrouracil, The presence of OGG2 type enzyme in bo th E. coli and eukaryotes, which is at least as efficient in excising G* fr om a G*.A (or G) pair as from a G*.C pair, supports the possibility of G* r epair in the nascent DNA strand.