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Title

Cloning, functional analysis and post-transcriptional regulation of a type II DNA topoisomerase from Leishmania infantum. A new potential target for anti-parasite drugs

AuthorsHanke, Tobias; Ramiro Ibáñez, M. J.; Trigueros, Sonia; Roca, Joaquim ; Larraga, Vicente
Issue Date2003
PublisherOxford University Press
CitationNucleic Acids Research, 2003, Vol. 31 (16) 4917-4928
AbstractWe identi®ed a type II topoisomerase enzyme from Leishmania infantum, a parasite protozoon causing disease in humans. This protein, named Li topo II, which displays a variable C-terminal end, is located in the kinetoplast. The cloned gene encoding Li- TOP2 compensates for the slow growth of topo IIde ®cient mutants of Saccharomyces cerevisiae, resulting in a catalytically active DNA topoisomerasein yeast. Analysis of the speci®c mRNA levels of the Li-TOP2 gene showed variations throughout the parasite cell cycle in synchronized cells as well as between the distinct forms of the parasite. Thus, the enzyme had higher levels of mRNA expression in the highly infective intracellular form of the parasite, the amastigote, than in the extracellular promastigote form, suggesting a relation with the distinct developmental and infectious phases of the protozoon. In addition, western blot analysis showed differences in protein expression between the proliferative and non-proliferative forms of L.infantum promastigotes, which displayed similar levels of mRNA. This indicated possible post-transcriptional regulation mechanisms. The data suggest that Li topo II has a part in DNA decatenation and probably at the initial stages of proliferation in the intracellular form of L.infantum, a parasite that has to proliferate into the host macrophage to survive its hostile environment in its ®rst moments of intracellular infection.
Description12 p.-7 fig.
Publisher version (URL)http://dx.doi.org/10.1093/nar/gkg671
URIhttp://hdl.handle.net/10261/103052
DOI10.1093/nar/gkg671
ISSN0305-1048
E-ISSN1362-4962
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