title: Involvement of TatD nuclease during programmed cell death in the protozoan parasite Trypanosoma brucei.
abstract: In this report, we describe the involvement of TatD nuclease during programmed cell death (PCD) in the human protozoan parasite Trypanosoma brucei. T. brucei TatD nuclease showed intrinsic DNase activity, was localized in the cytoplasm and translocated to the nucleus when cells were treated with inducers previously demonstrated to cause PCD in T. brucei. Overexpression of TatD nuclease resulted in elevated PCD and conversely, loss of TatD expression by RNAi conferred significant resistance to the induction of PCD in T. brucei. Co-immunoprecipitation studies revealed that TatD nuclease interacts with endonucleaseG suggesting that these two nucleases could form a DNA degradation complex in the nucleus. Together, biochemical activity, RNAi and subcellular localization results demonstrate the role of TatD nuclease activity in DNA degradation during PCD in these evolutionarily ancient eukaryotic organisms. Further, in conjunction with endonucleaseG, TatD may represent a critical nuclease in a caspase-independent PCD pathway in trypanosomatid parasites since caspases have not been identified in these organisms.
authors.affiliation: Laboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, MD 20892, USA.
authors.forename: Sreenivas
authors.initials: S
authors.lastname: Gannavaram
authors.forename: Alain
authors.initials: A
authors.lastname: Debrabant
mesh_terms: D017209:Apoptosis; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D053938:DNA Fragmentation; D016054:DNA, Protozoan / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D014346:Trypanosoma brucei brucei / Q000166:cytology* / Q000235:genetics / Q000378:metabolism
chemical_list: D016054:DNA, Protozoan; D015800:Protozoan Proteins; D004706:Endodeoxyribonucleases; C052391:endonuclease G