PMID: 9428797Jan 15, 1998Paper

Topoisomerase II inhibitors induce cleavage of nuclear and 35-kb plastid DNAs in the malarial parasite Plasmodium falciparum

DNA and Cell Biology
V WeissigT C Rowe

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.

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