Document Type: Review Article


1 Young Researchers and Elite Club, Baft Branch, Islamic Azad University, Baft, Iran

2 Department of Chemistry, Faculty of Science, Imam Khomeini International University, Qazvin, Iran


Objective: In this paper, we have introduced topoisomerase inhibitors, mechanism of action and types of them. DNA topoisomerases are ubiquitous enzymes that catalyze essential enzymes to solve the topological problems accompanying key nuclear processes such as DNA replication, transcription, repair and chromatin assembly by introducing temporary single or double strand breaks in the DNA. Results: There are two types of DNA topoisomerase: I and II, which are enzymes that control the changes in DNA structure by catalyzing the breaking and rejoining of the phosphodiester backbone of DNA strands during the normal cell cycle. Topoisomerases are crucial for the several DNA functions (e.g. replication and transcription) that require the DNA to be unravelled, a process that generates tension and entanglement in DNA. Topoisomerase I breaks a single DNA strand while topoisomerase II breaks both strands and requires ATP for full activity.  In  both  cases,  the  enzyme  is covalently  attached  to  the  DNA  through tyrosine residues in the active site.


Wang, J. C. (1996). DNA topoisomerases. Annu. Rev. Biochem. 65: 635-692.
Champoux, J. J. (2001). DNA topoisomerases: structure, function, and mechanism. Annu. Rev. Biochem. 70: 369-413.
Jaxel, C., Nadal, M., Mirambeau, G., Forterre, P., Takahashi, M., and Duguet, M. (1989). Reverse gyrase inding to DNA alters the double helix structure and
produces single-strand cleavage in the absence of ATP. EMBO J. 8: 3135-3139.
Denny, W. A. (2004). Emerging DNA topisomerase inhibitors as anticancer drugs. Exp. Opin. Emerg. Drugs. 9: 105-133.
Kaufmann, W. K. (1998). Human topoisomerase II function, tyrosine phosphorylation and cell cycle checkpoints. Proc. Soc. Exp. Biol. Med. 217: 327-334.
Hengstler, J. G., Heimerdinger, C. K., Schiffer, I. B., Gebhard, S., Sagemuller, J., Tanner, B., Bolt, H. M., and Oesch, F. (2002). Dietary topoisomerase-II poisons: contribution of soy products to infant leukemia. EXCLI J. 1: 8-14.
Burden, D. A., and Osheroff, N. (1998). Mechanism of action of eukaryotic topoisomerase II and drugs targeted to the enzyme. Biochem. Biophys. Acta. 1400:139-154.
Holden, J. A. (2001). DNA topoisomerases as anticancer drug targets: from the laboratory to the clinic. Curr. Med. Chem. Anticancer Agents. 1: 1-25.
Larsen, A. K., Escargueil, A. E., and Skladanowski, A. (2003). Catalytic topoisomerase II inhibitors in cancer therapy. Pharmacol. Ther. 99: 167-181.
Andoh, T., and Ishida, R. (1998). Catalytic inhibitors of DNA topoisomerase. Biochim. Biophys. Acta. 1400: 155-171.
Denny, W. A. (1997). Dual topoisomerase I/II poisons as anticancer drugs. Expert Opin. Invest. Drugs. 6: 1845-1851.
Denny, W. A., and Baguley, B. C. (2003). Dual topoisomerase I/II inhibitors in cancer therapy. Curr. Top. Med. Chem. 3: 339-353.
Sordet, O., Khan, Q. A., Kohn, K. W., and Pommier, Y. (2003). Apoptosis induced by topoisomerase inhibitors. Curr. Med. Chem. Anticancer Agents. 3: