Yi. Pavlov et al., BASE ANALOG N-6-HYDROXYLAMINOPURINE MUTAGENESIS IN ESCHERICHIA-COLI -GENETIC-CONTROL AND MOLECULAR SPECIFICITY, Mutation research, 357(1-2), 1996, pp. 1-15
We have studied the molecular specificity of the base analog N-6-hydro
xylaminopurine (HAP) in the E. coli lad gene, as well as the effects o
f mutations in DNA repair and replication genes on HAP mutagenesis. HA
P induced base substitutions of the two transition types (A . T-->G .
C and G . C-->A . T) at equal frequency. This bi-directional transitio
n specificity is consistent with in vitro primer extension experiments
with the Klenow fragment of DNA polymerase I in which we observed tha
t either dTTP or dCTP were incorporated opposite HAP in an oligonucleo
tide template. The spectrum of HAP-induced transitions was different f
rom the spontaneous transitions in either a wild-type or a mismatch-re
pair-defective (mutL) strain. Mutations in genes controlling excision
repair, exonucleolytic proofreading, mismatch correction, error-prone
(SOS) repair and 8-oxo-guanine repair did not affect HAP-induced mutag
enesis substantially, However, an extensive deletion of several genes
in the uvrB-bio region conferred supersensitivity to the lethal and mu
tagenic effects of HAP, perhaps due to an effect on HAP metabolism. dn
aE antimutator alleles reduced HAP-forward mutagenicity in allele-spec
ific manner: dnaE911 reduced it several fold, while dnaE915 abolished
it almost completely. The results obtained are consistent with the ide
a that HAP is mutagenic in E. coli via a pathway generating replicatio
n errors.