{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Obado SO"],"funding":["FIC NIH HHS","Biotechnology and Biological Sciences Research Council"],"pagination":["1023-33"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3035458"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["39(3)"],"pubmed_abstract":["Topoisomerase-II accumulates at centromeres during prometaphase, where it resolves the DNA catenations that represent the last link between sister chromatids. Previously, using approaches including etoposide-mediated topoisomerase-II cleavage, we mapped centromeric domains in trypanosomes, early branching eukaryotes in which chromosome segregation is poorly understood. Here, we show that in bloodstream form Trypanosoma brucei, RNAi-mediated depletion of topoisomerase-IIα, but not topoisomerase-IIβ, results in the abolition of centromere-localized activity and is lethal. Both phenotypes can be rescued by expression of the corresponding enzyme from T. cruzi. Therefore, processes which govern centromere-specific topoisomerase-II accumulation/activation have been functionally conserved within trypanosomes, despite the long evolutionary separation of these species and differences in centromeric DNA organization. The variable carboxyl terminal region of topoisomerase-II has a major role in regulating biological function. We therefore generated T. brucei lines expressing T. cruzi topoisomerase-II truncated at the carboxyl terminus and examined activity at centromeres after the RNAi-mediated depletion of the endogenous enzyme. A region necessary for nuclear localization was delineated to six residues. In other organisms, sumoylation of topoisomerase-II has been shown to be necessary for regulated chromosome segregation. Evidence that we present here suggests that sumoylation of the T. brucei enzyme is not required for centromere-specific cleavage activity."],"journal":["Nucleic acids research"],"pubmed_title":["Centromere-associated topoisomerase activity in bloodstream form Trypanosoma brucei."],"pmcid":["PMC3035458"],"funding_grant_id":["BB/C501292/1","D43TW007888"],"pubmed_authors":["Alvarez VE","Kelly JM","Taylor MC","Echeverry MC","Obado SO","Bot C","Bayona JC"],"additional_accession":[]},"is_claimable":false,"name":"Centromere-associated topoisomerase activity in bloodstream form Trypanosoma brucei.","description":"Topoisomerase-II accumulates at centromeres during prometaphase, where it resolves the DNA catenations that represent the last link between sister chromatids. Previously, using approaches including etoposide-mediated topoisomerase-II cleavage, we mapped centromeric domains in trypanosomes, early branching eukaryotes in which chromosome segregation is poorly understood. Here, we show that in bloodstream form Trypanosoma brucei, RNAi-mediated depletion of topoisomerase-IIα, but not topoisomerase-IIβ, results in the abolition of centromere-localized activity and is lethal. Both phenotypes can be rescued by expression of the corresponding enzyme from T. cruzi. Therefore, processes which govern centromere-specific topoisomerase-II accumulation/activation have been functionally conserved within trypanosomes, despite the long evolutionary separation of these species and differences in centromeric DNA organization. The variable carboxyl terminal region of topoisomerase-II has a major role in regulating biological function. We therefore generated T. brucei lines expressing T. cruzi topoisomerase-II truncated at the carboxyl terminus and examined activity at centromeres after the RNAi-mediated depletion of the endogenous enzyme. A region necessary for nuclear localization was delineated to six residues. In other organisms, sumoylation of topoisomerase-II has been shown to be necessary for regulated chromosome segregation. Evidence that we present here suggests that sumoylation of the T. brucei enzyme is not required for centromere-specific cleavage activity.","dates":{"release":"2011-01-01T00:00:00Z","publication":"2011 Feb","modification":"2025-04-19T21:38:57.297Z","creation":"2019-03-27T00:38:46Z"},"accession":"S-EPMC3035458","cross_references":{"pubmed":["20864447"],"doi":["10.1093/nar/gkq839"]}}