View article

DNA topoisomerases I and II (Top1 and Top2) are established molecular targets of anticancer drugs. 1-5 Mammalian somatic cells express six topoisomerase genes: two TOP1 (TOP1 and TOP1mt), two TOP2 (TOP2R and), and two topoisomerase III (TOP3R and) 6, 7 (Figure 1A). The most recently discovered eukaryotic topoisomerase is mitochondrial Top1 (Top1mt), which we reported in 2001. 8, 9 A common feature of topoisomerases is their catalytic mechanism, which in all cases consists in a nucleophilic attack of a DNA phosphodiester bond by a catalytic tyrosyl residue from the topoisomerase. The resulting covalent attachment of the tyrosine to the DNA phosphate is either at the 3′-end of the broken DNA in the case of Top1 enzymes (Top1 and Top1mt) or at the 5′-end of the broken DNA for the other topoisomerases (Figure 1). Thus, Top1 enzymes are the only topoisomerases that form a covalent link with …