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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todo:paper_00207519_v41_n3_p405_VilchezLarrea2023-10-03T14:18:36Z Poly(ADP-ribose) polymerase plays a differential role in DNA damage-response and cell death pathways in Trypanosoma cruzi Vilchez Larrea, S.C. Alonso, G.D. Schlesinger, M. Torres, H.N. Flawiá, M.M. Fernández Villamil, S.H. 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 Trypanosoma cruzi ultraviolet radiation Animals Cell Death Cell Nucleus DNA Damage DNA Repair Glycoside Hydrolases Poly(ADP-ribose) Polymerases Protozoan Proteins Trypanosoma cruzi Eukaryota Protista 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 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. Fil:Alonso, G.D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Torres, H.N. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Flawiá, M.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00207519_v41_n3_p405_VilchezLarrea |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
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 Trypanosoma cruzi ultraviolet radiation Animals Cell Death Cell Nucleus DNA Damage DNA Repair Glycoside Hydrolases Poly(ADP-ribose) Polymerases Protozoan Proteins Trypanosoma cruzi Eukaryota Protista Trypanosoma cruzi |
spellingShingle |
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 Trypanosoma cruzi ultraviolet radiation Animals Cell Death Cell Nucleus DNA Damage DNA Repair Glycoside Hydrolases Poly(ADP-ribose) Polymerases Protozoan Proteins Trypanosoma cruzi Eukaryota Protista Trypanosoma cruzi Vilchez Larrea, S.C. Alonso, G.D. Schlesinger, M. Torres, H.N. Flawiá, M.M. Fernández Villamil, S.H. Poly(ADP-ribose) polymerase plays a differential role in DNA damage-response and cell death pathways in Trypanosoma cruzi |
topic_facet |
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 Trypanosoma cruzi ultraviolet radiation Animals Cell Death Cell Nucleus DNA Damage DNA Repair Glycoside Hydrolases Poly(ADP-ribose) Polymerases Protozoan Proteins Trypanosoma cruzi Eukaryota Protista Trypanosoma cruzi |
description |
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. |
format |
JOUR |
author |
Vilchez Larrea, S.C. Alonso, G.D. Schlesinger, M. Torres, H.N. Flawiá, M.M. Fernández Villamil, S.H. |
author_facet |
Vilchez Larrea, S.C. Alonso, G.D. Schlesinger, M. Torres, H.N. Flawiá, M.M. Fernández Villamil, S.H. |
author_sort |
Vilchez Larrea, S.C. |
title |
Poly(ADP-ribose) polymerase plays a differential role in DNA damage-response and cell death pathways in Trypanosoma cruzi |
title_short |
Poly(ADP-ribose) polymerase plays a differential role in DNA damage-response and cell death pathways in Trypanosoma cruzi |
title_full |
Poly(ADP-ribose) polymerase plays a differential role in DNA damage-response and cell death pathways in Trypanosoma cruzi |
title_fullStr |
Poly(ADP-ribose) polymerase plays a differential role in DNA damage-response and cell death pathways in Trypanosoma cruzi |
title_full_unstemmed |
Poly(ADP-ribose) polymerase plays a differential role in DNA damage-response and cell death pathways in Trypanosoma cruzi |
title_sort |
poly(adp-ribose) polymerase plays a differential role in dna damage-response and cell death pathways in trypanosoma cruzi |
url |
http://hdl.handle.net/20.500.12110/paper_00207519_v41_n3_p405_VilchezLarrea |
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