title: Poly(ADP-ribose) polymerase plays a differential role in DNA damage-response and cell death pathways in Trypanosoma cruzi.
abstract: Poly(ADP-ribosyl)ation is a post-translational modification of proteins. Poly(ADP-ribose) polymerase (PARP) and poly(ADP-ribose) glycohydrolase (PARG) are the enzymes responsible for poly(ADP-ribose) (PAR) polymer metabolism and are present in most higher eukaryotes. The best understood role of PARP is the maintenance of genomic integrity either via promotion of DNA repair at low levels of genotoxic stress or via promotion of cell death at higher levels of damage. The unicellular eukaryote Trypanosoma cruzi, as opposed to humans and other organisms, has only one PARP (TcPARP) and one PARG (TcPARG). In the present study we show that under different DNA-damaging agents (H(2)O(2) or UV-C radiation) TcPARP is activated and translocated from the cytosol to the nucleus, while TcPARG always shows a nuclear localisation. Parasites in the presence of PARP or PARG inhibitors, as well as parasites over-expressing either TcPARP or TcPARG, suggested that PAR metabolism could be involved in different phases of cell growth, even in the absence of DNA damage. We also believe that we provide the first reported evidence that different proteins could be poly(ADP-ribosyl)ated in response to different stimuli, leading to different cell death pathways.
authors.affiliation: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Vuelta de Obligado 2490, Ciudad Autónoma de Buenos Aires, 1428 Buenos Aires, Argentina.
authors.forename: Salomé C
authors.initials: SC
authors.lastname: Vilchez Larrea
authors.forename: Guillermo D
authors.initials: GD
authors.lastname: Alonso
authors.forename: Mariana
authors.initials: M
authors.lastname: Schlesinger
authors.forename: Héctor N
authors.initials: HN
authors.lastname: Torres
authors.forename: Mirtha M
authors.initials: MM
authors.lastname: Flawiá
authors.forename: Silvia H
authors.initials: SH
authors.lastname: Fernández Villamil
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D006026:Glycoside Hydrolases / Q000235:genetics / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development / Q000502:physiology
chemical_list: D015800:Protozoan Proteins; D011065:Poly(ADP-ribose) Polymerases; D006026:Glycoside Hydrolases; C022407:poly ADP-ribose glycohydrolase