Poly(ADP-ribose) polymerase plays a differential role in DNA damage-response and cell death pathways in Trypanosoma cruzi

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...

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Detalles Bibliográficos
Autores principales: Vilchez Larrea, S.C., Alonso, G.D., Schlesinger, M., Torres, H.N., Flawiá, M.M., Fernández Villamil, S.H.
Formato: JOUR
Materias:
Cell death
DNA repair
PARG
PARP
Trypanosoma cruzi
hydrogen peroxide
nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase
DNA
eukaryote
genotoxicity
inhibitor
metabolism
parasite
polymerase chain reaction
protein
apoptosis
article
cell growth
cell nucleus
controlled study
cytosol
DNA damage
enzyme activation
enzyme activity
gene translocation
nonhuman
nuclear localization signal
nucleotide sequence
protein expression
ultraviolet radiation
Animals
Cell Death
Cell Nucleus
DNA Damage
DNA Repair
Glycoside Hydrolases
Poly(ADP-ribose) Polymerases
Protozoan Proteins
Eukaryota
Protista
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_00207519_v41_n3_p405_VilchezLarrea
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario: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 (H2O2 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. © 2010 Australian Society for Parasitology Inc.

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