Increased binding of ethidium bromide to polynucleotide duplexes containing mismatched bases

The binding of the intercalating dye ethidium bromide to a series of synthetic polynucleotide duplexes containing varying concentrations of mismatched bases has been measured by fluorescence titration. The dye binds more strongly to duplexes with mismatches, the estimated increase in affinity being twenty-fold for the series of molecules poly (I).poly (C,Ax) with x denoting the mole fraction of mismatched A residues in the C strand. The results are consistent with one requirement of the Streisinger model for frameshift mutagenesis, namely that frameshifting agents can function by stablizing mismatched transient intermediates in DNA.