title: A possible mechanism for an interaction between postreplication recombination repair and base misincorporation in mutation induction by N-methyl-N'-nitro-N-nitrosoguanidine in Haemophilus influenzae.
abstract: Evidence in previous publications has suggested that treatment with monofunctional alkylating agents such as N-methyl-N'-nitro-nitrosoguanidine (MNNG) results in gaps being left in the DNA synthesized shortly after the treatment. This paper presents further evidence that suggests, though it does not conclusively prove, that there are indeed gaps. It shows that these events increase linearly with MNNG concentration, that they are formed mainly in DNA synthesized during the first hour after treatment, and that only a few are formed at later times. An hypothesis that involves the conversion by recombination repair of a single-strand base substitution, resulting from insertion of an incorrect base opposite an alkylated base, to a double-strand base substitution is proposed. It is suggested that most single-strand substitutions are removed by mismatch repair, leaving  the double-strand substitutions as the main source of mutations. This hypothesis predicts that the mutation frequency will increase as the square of the exposure to MNNG, and this seems to be the case, at least at lower exposures at which complicating factors such as lengthened expression time are avoided. It also can explain a number of earlier observations on mutation fixation as detected by transformation. An attempt to show that the non-coding lesions causing the gaps were apurinic sites was unsuccessful.
mesh_terms: D002499:Centrifugation, Density Gradient; D002845:Chromatography; D004260:DNA Repair / Q000187:drug effects*; D004269:DNA, Bacterial / Q000096:biosynthesis; D004277:DNA, Single-Stranded / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D006193:Haemophilus influenzae / Q000187:drug effects / Q000235:genetics*; D006863:Hydrogen-Ion Concentration; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology*; D008957:Models, Genetic; D009154:Mutation; D011995:Recombination, Genetic / Q000187:drug effects*
chemical_list: D004269:DNA, Bacterial; D004277:DNA, Single-Stranded; D008769:Methylnitronitrosoguanidine