Cellular and organism aging have been correlated with accumulated DNA
damage (1,2). 8-oxo-7,8-dihydrodeoxyguanine (8-oxoG or GO) is one of the
most stable products of oxidative DNA damage. The formation of GO in DNA,
if not repaired, can lead to misincorporation of A opposite to the GO lesion and
result in G:C to T:A transversions (3–6). In Escherichia coli, a family of
enzymes, MutY, MutM, and MutT, is involved in defending against the
mutagenic effects of GO lesions (7–9). The E. coli MutY is an adenine glycosylase
active on DNA containing A/GO, A/G, and A/C mismatches (7,10–15) and also has
a weak guanine glycosylase activity on G/GO-containing DNA (15a,15b).
MutY removes misincorporated adenines paired with GO lesions and reduces
the GO mutational effects. The 39-kDa MutY protein from E. coli is an ironsulfur
protein. The MutY protein was shown by Tsai-Wu et al. (16) to have
both DNA glycosylase and apurinic/apyrimidinic (AP) lyase activities. Recent
results show that MutY and the N-terminal catalytic domain can be trapped in
a stable covalent enzyme-DNA intermediate in the presence of sodium borohydride
(17–19) and support that MutY contains both DNA glycosylase and
AP lyase activities. The DNA glycosylase activity removes the adenine bases
from the A/GO, A/G, and A/C mismatches (16) and the AP lyase activity
cleaves the first phosphodiester bond 3' to the AP site (12,16). Apparent
dissociation constants are 0.066, 5.3, and 15 nM for A/GO-, A/G-, and A/Ccontaining
DNA, respectively (20).