Our lab is interested in the cellular function of nuclear and organellar DNA topoisomerases and their role as targets for cancer and malarial chemotherapy. DNA topoisomerases are an ubiquitous class of enzymes which regulate the structure and function of cellular chromosomes. These enzymes are also targets of important anticancer (e.g., anthracyclines, epipodophyllotoxins, amsacrines, and camptothecins) and antimicrobial (fluoroquinolone) drugs. Most recently, our efforts have focused on the identification of a type II topoisomerase that is associated with the novel 35 kb circular plastid DNA of the malarial parasite P. falciparum. The 35 kb plastid DNA is thought to be localized within the apicoplast, a non-photosynthetic plastid an organelle of unknown function which has no counterpart in mammalian cells. Pharmacologic and genetic evidence indicate that the topoisomerase activity associated with the 35 kb plastid DNA is related to the bacterial type II topoisomerase DNA gyrase. We are currently investigating whether this novel topoisomerase might provide a selective target for the development of new antimalarial drugs. We are also interested in identifying the role of this unusual topoisomerase in the regulation of the novel 35 kb plastid genome of malaria.
- Jahn SC, Law ME, Corsino PE, Rowe TC, Davis BJ, Law BK. Assembly, activation, and substrate specificity of cyclin D1/Cdk2 complexes. Biochemistry. 2013 May 21;52(20):3489-501. doi: 10.1021/bi400047u. Epub 2013 May 9.
- Ostrov DA, Hernández Prada JA, Corsino PE, Finton KA, Le N, Rowe TC. Discovery of novel DNA gyrase inhibitors by high-throughput virtual screening. Antimicrob Agents Chemother. 2007 Oct;51(10):3688-98. Epub 2007 Aug 6.