Mechanism of action of eukaryotic DNA topoisomerase I and drugs targeted to the enzyme

Biochim Biophys Acta. 1998 Oct 1;1400(1-3):83-105. doi: 10.1016/s0167-4781(98)00129-8.


DNA topoisomerase I is essential for cellular metabolism and survival. It is also the target of a novel class of anticancer drugs active against previously refractory solid tumors, the camptothecins. The present review describes the topoisomerase I catalytic mechanisms with particular emphasis on the cleavage complex that represents the enzyme's catalytic intermediate and the site of action for camptothecins. Roles of topoisomerase I in DNA replication, transcription and recombination are also reviewed. Because of the importance of topoisomerase I as a chemotherapeutic target, we review the mechanisms of action of camptothecins and the other topoisomerase I inhibitors identified to date.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Camptothecin / pharmacology*
  • Camptothecin / therapeutic use
  • DNA / metabolism
  • DNA Topoisomerases, Type I / physiology*
  • Drug Resistance / genetics
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Intercalating Agents / chemistry
  • Intercalating Agents / pharmacology
  • Models, Molecular
  • Molecular Structure
  • Polycyclic Compounds / chemistry
  • Polycyclic Compounds / pharmacology
  • Topoisomerase I Inhibitors


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Intercalating Agents
  • Polycyclic Compounds
  • Topoisomerase I Inhibitors
  • DNA
  • DNA Topoisomerases, Type I
  • Camptothecin