Chemical agents able to interfere with
DNA topoisomerases are widespread in nature, and some of them have outstanding therapeutic efficacy in human
cancer and
infectious diseases.
DNA topoisomerases are essential
enzymes that govern
DNA topology during fundamental nuclear metabolic processes. Topoisomerase-interfering compounds can be divided into two general categories based on the mechanism of
drug action:
poisons and catalytic inhibitors. In past years, investigations of the DNA sequence selectivity of
topoisomerase II poisons have identified structural and molecular determinants of
drug activity, and indicated that the
drug receptor is likely to be at the
protein-
DNA interface. Moreover, the available results indicate that the biologically relevant
DNA-binding activity of topoisomerase
poisons is basically
protein-mediated and this is discussed in this issue by Giovanni Capranico and colleagues. This suggests that topoisomerase
poisons may represent a useful paradigm for small compounds able to bind to
protein-
DNA interfaces in a site-selective manner, thus increasing the affinity of
DNA-binding proteins for specific genomic sites.