DNA topoisomerases: from a laboratory curiosity to a subject in cancer chemotherapy.

Recent studies indicate that the type II DNA topoisomerases of eubacteria and eukaryotes are structurally and evolutionarily related: the amino and carboxyl half of the single polypeptide eukaryotic enzyme are homologous to the B and A subunit of bacterial gyrase, respectively. The active site tyrosine of Escherichia coli DNA gyrase that becomes covalently linked to DNA during catalysis has been identified to be Tyr 122 of the A subunit. From a comparison of nucleotide sequences of the structural genes encoding several other type II topoisomerases, the active site tyrosine in these enzymes can be deduced. For the type I DNA topoisomerases, although the bacterial enzyme and the eukaryotic enzyme are very different in terms of their primary structures, substrate preferences, and mechanisms, it has been shown that the yeast DNA topoisomerase I can substitute for E. coli DNA topoisomerase I in vivo. The unique features of DNA topoisomerases as targets of antibiotics and anti-tumor drugs are discussed.