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

• Published in: International journal for parasitology 2011-03, Vol.41 (3-4), p.405-416
• Main Authors: Vilchez Larrea, Salomé C., Alonso, Guillermo D., Schlesinger, Mariana, Torres, Héctor N., Flawiá, Mirtha M., Fernández Villamil, Silvia H.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell death; Cell Death - physiology; Cell Nucleus - metabolism; DNA Damage; DNA Repair; Fundamental and applied biological sciences. Psychology; Glycoside Hydrolases - genetics; Glycoside Hydrolases - metabolism; Life cycle. Host-agent relationship. Pathogenesis; PARG; PARP; Poly(ADP-ribose) Polymerases - genetics; Poly(ADP-ribose) Polymerases - metabolism; Protozoa; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Trypanosoma cruzi; Trypanosoma cruzi - enzymology; Trypanosoma cruzi - genetics; Trypanosoma cruzi - growth & development; Trypanosoma cruzi - physiology
• ISSN: 0020-7519; 1879-0135
• DOI: 10.1016/j.ijpara.2010.11.008

[Display omitted] ► Trypanosoma cruzi poly(ADP-ribose) polymerase (PARP) translocates to the nucleus in response to DNA damage. ► PAR metabolism is involved in at least two DNA strand break signalling pathways. ► PARP is connected with different cell death programs. ► Different DNA damaging agents induce distinct patterns of PARylated proteins. 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.