Mechanisms of Spontaneous and Induced Frameshift Mutation in Bacteriophage T4

Frequencies of spontaneous and proflavine-induced frameshift mutations increased dramatically as a function of the number of reiterated base pairs at each of two sites in the lysozyme gene of bacteriophage T4. At each site, proflavine induces addition mutations more frequently than deletion mutations. We confirm that the steroidal diamine, irehdiamine A, induces frameshift addition mutations. At sites of reiterated bases, we propose that base pairing is misaligned adjacent to a gap. The misaligned configuration is stabilized by the stacking of mutagen molecules around the extrahelical base, forming a sandwich. Proflavine induces addition mutations efficiently at a site without any reiterated bases. Mutagenesis at such sites may be due to mutagen-induced stuttering of the replication complex.