Model for the participation of quasi-palindromic DNA sequences in frameshift mutation.

Abstract

A model is described for the templated production of frameshift and base-substitution mutations mediated through aberrant DNA structures arising as a consequence of quasi-palindromic DNA sequences. Two general mechanisms are considered. One evokes the formation and processing of imperfect DNA secondary structures (hairpins) for the production of mutations. The other evokes a "strand switch" during DNA synthesis which, in a manner unique to quasi-palindromic sequences, may be resolved to produce frameshift or base-substitution mutations, or both. It is the unique combination of symmetrical and asymmetrical elements of the quasi-palindromic sequence itself that provides the basis for both models. Through the mechanisms described, the symmetrical elements permit unusually paired DNA substrates, and the asymmetrical elements permit templated insertions, deletions, and base substitutions. The model predicts a class of mutations--simultaneously frameshifts and base substitutions--whose sequences can be predicted from a local quasi-palindromic sequence. This prediction appears to be met by a significant fraction (more than 15%) of frameshift mutations in the iso-1-cytochrome c gene of Saccharomyces cerevisiae.