The role of polyamines in the function of DNA is multifaceted. As polyamines bind to DNA, DNA conformation changes and therefore DNA binding affinity of gene regulatory proteins is modulated. Certain DNA conformational variations enhance protein binding, whereas others inhibit protein-DNA interactions. Certain protein-binding sites might be masked by polyamines, which will be unmasked by acetylation of polyamines, relieving polyamine interactions with DNA. Thus, the binding of polyamines to DNA introduces a dynamic role in gene expression as polyamine levels are exquisitely regulated by biosynthetic and catabolic enzymes and by uptake/efflux pathways. These direct effects of polyamines on gene regulation will be in addition to the effects of polyamines on cell signaling pathways and kinase activities. Thus there are numerous opportunities that need to be explored in controlling gene expression, cell-cycle regulation, and malignant cell growth by interfering with cellular regulation of polyamines.
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