Oligonucleotide-Directed DNA Triple-Helix Formation: An Approach to Artificial Repressors?

Abstract

Pyrimidine oligonucleotides exhibit sequence-specific binding to purine sequences in double-helical DNA. Molecular recognition occurs through triple-helix formation, mediated by Hoogsteen hydrogen bonding of the pyrimidine strand parallel to the double-helical DNA purine strand. Oligonucleotide-directed DNA triple-helix formation has been shown to inhibit the recognition of double-helical DNA by sequence-specific binding proteins. This observation provides the potential for new approaches to both the analysis of nucleic acids, and the study of nucleic acid-protein interactions. We wish to understand molecular mechanisms whereby such complexes affect protein-DNA interactions involved in eukaryotic transcription.