Topoisomerase II Inhibitors Induce Cleavage of Nuclear and 35-kb Plastid DNAs in the Malarial ParasitePlasmodium falciparum
- 1 December 1997
- journal article
- research article
- Published by Mary Ann Liebert Inc in DNA and Cell Biology
- Vol. 16 (12), 1483-1492
- https://doi.org/10.1089/dna.1997.16.1483
Abstract
The topoisomerase II-specific inhibitors VP-16 and ciprofloxacin were used to investigate the presence of topoisomerase II activities associated with nuclear and 35-kb plastid DNAs of the malarial parasite Plasmodium falciparum. The eukaryotic topoisomerase II inhibitor VP-16 induced cleavage of both nuclear and 35-kb parasite DNAs. In contrast, ciprofloxacin, a fluoroquinolone drug known to act on the bacterial type II topoisomerase DNA gyrase, only induced cleavage of the Plasmodial 35-kb DNA. Drug-induced cleavage resulted in the protection of the 5′- but not 3′- ends of the cleaved nuclear and 35-kb DNAs from exonuclease digestion, suggesting that the 5′-ends of the broken DNA were protein-linked, a property reminiscent of DNA cleavage mediated by topoisomerase II enzymes. Furthermore, DNA cleavage induced by both VP-16 and ciprofloxacin was heat-reversible. This is the first evidence that P. falciparum contains two distinct topoisomerase II activities that are molecular targets for chemotherapeutic agents.Keywords
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