Role of Polyamines in Regulation of Sequence-Specific DNA Binding Activity

Abstract

Polyamines are positively charged under physiological ionic and pH conditions. Therefore, the negatively charged macromolecules in the cell, DNA, RNA, and certain proteins are natural targets for their interaction. Polyamine interaction with DNA was considered to be electrostatic in nature and was theoretically interpreted in terms of the counterion condensation theory. Early studies suggested stabilization of duplex DNA by natural and synthetic polyamines, independent of the chemical structure of the polyamine or the sequence of the DNA. More recent studies have revealed polyamine structural specificity, as well as DNA sequence specificity, in addition to the overriding electrostatic interaction. Studies using photoaffinity probes indicate preferential binding of polyamines to bent adenine tracts and TATA elements, suggesting their involvement in the regulation of gene expression. Molecular modeling and experimental studies also indicate sequencespecific binding to GC-rich major grooves. DNA sequence-specific binding of polyamines might also be important in polyamine-induced facilitation of DNA-protein interactions, observed with several transcription factors. The unique contact sites in the interactions between DNA and polyamines are attested by polyamine structural specificity evident in DNA conformational transitions, DNA nanoparticle formation, triplex DNA stabilization, and DNA·RNA hybrid stability. Both polyamine structural specificity and DNA sequence specificity may find applications in polyamine-based drug design, bionanotechnology, and in understanding the mechanism of gene regulation.