PMID: 9164874May 15, 1997Paper

Molecular cloning and expression of the Candida albicans TOP2 gene allows study of fungal DNA topoisomerase II inhibitors in yeast

The Biochemical Journal
B A KellerL M Fisher

Abstract

Candida albicans topoisomerase II, encoded by the TOP2 gene, mediates chromosome segregation by a double-strand DNA break mechanism and is a potential target for anti-fungal therapy. In this paper, we report the characterization of the C. albicans TOP2 gene and its use to develop a yeast system that allows the identification and study of anti-fungal topoisomerase II inhibitors in vivo. The gene, specifying a 1461-residue polypeptide with only 40% identity with human topoisomerase IIalpha and beta isoforms, was isolated from C. albicans on a 6.3 kb EcoRI fragment that mapped to chromosome 4. It was used to construct a plasmid in which TOP2 expresses a recombinant enzyme (residues 57-1461 of C. albicans topoisomerase II fused to the first five residues of Saccharomyces cerevisiae topoisomerase II) under the control of a galactose-inducible promoter. The plasmid rescued the lethal phenotype of a temperature-sensitive S. cerevisiae DNA topoisomerase II mutant allowing growth at 35 degrees C. Yeast cells, bearing ISE2 permeability and rad52 double-strand-break-repair mutations the growth of which at 35 degrees C was dependent on C. albicans topoisomerase II, were killed by the known topoisomerase II inhibitors amsacrine and doxorubi...Continue Reading

Citations

Feb 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·Q Liu, J C Wang
Dec 29, 2011·Molecular and Cellular Biochemistry·Hao Zheng, Yong-Sheng Yu
Sep 24, 2011·Medical Mycology·Dietmar SteverdingSilke Schelenz
Jul 5, 2005·Expert Opinion on Therapeutic Targets·J A Simon
May 23, 2002·Antimicrobial Agents and Chemotherapy·Shabana I KhanAlice M Clark
Oct 23, 1998·Microbiology·Hironobu NakayamaKunio Kitada

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