Base substitution mutations induced in the cI gene of lambda phage by neocarzinostatin chromophore: correlation with depyrimidination hotspots at the sequence AGC.
Treatment of intact lambda phage with the nonprotein chromophore of neocarzinostatin resulted in efficient phage inactivation and generation of clear-plaque mutants. Both effects required a preincubation at low pH to allow diffusion of chromophore into the phage head. Chromophore activation was then effected by addition of a sulfhydryl cofactor, followed by a shift to neutral pH. Sequence analysis of mutations mapped to the DNA-binding region of the cI gene revealed that nearly all were single base substitutions. Significant numbers of all possible base changes were found, with A:T to G:C transitions being the most frequent events. Of 11 G:C to A:T transitions, 7 were found at C residues in the trinucleotide sequence AGC, which has previously been shown to be a hotspot for chromophore-induced depyrimidination. This result, as well as the SOS dependence of mutagenesis and the overall distribution of various types of base substitutions, is consistent with the hypothesis that apurinic/apyrimidinic sites are important mutagenic lesions.
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D010582:Bacteriophage lambda / Q000187:drug effects / Q000235:genetics; D001483:Base Sequence; D005814:Genes, Viral; D009154:Mutation / Q000187:drug effects*; D014764:Viral Proteins / Q000235:genetics; D009353:Zinostatin / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D014764:Viral Proteins; D009353:Zinostatin