Poly(ADP-ribosyl)ation in cell cycle and DNA damage signaling in Trypanosoma cruzi

VILCHEZ LARREA, SC.; ALONSO, GD.; TORRES, HN.; FLAWIÁ, MM.; FERNÁNDEZ VILLAMIL, SH.

Villa Carlos Paz. Cordoba, Argentina.

Congreso; XLIV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB).; 2008

Poly(ADP-ribosyl)ation of different proteins is important for chromatin remodeling, an essential process that occurs in physiological and pathological conditions. The nuclear enzyme poly(ADP-ribose)polymerase (PARP) is able to transfer ADP-ribose from NAD+ to target proteins, forming polymers (PAR) in response to DNA single strand breaks. In Trypanosoma cruzi only one PARP (TcPARP) has been identified. We have shown that TcPARP is present in all developmental stages of this parasite and, upon recognition of sbDNA, it activates, triggering an automodification reaction. Our aim is to study the role of TcPARP in chromatin dynamic structural changes throughout the cell cycle as well as in damage signaling. In synchronized cells, PARP content seems to be constant during cell cycle but PAR levels are high at G1 phase, then decrease to rise again in the late S and G2 phases. Regarding its role in DNA damage signaling, exposure of epimastigotes to UV radiation or H2O2, triggers the formation of PAR in a time exposition- or concentration-dependent manner. Post-injury survival assays have shown that the inhibition of TcPARP can allow the cells to avoid death when subjected to long UV irradiation times. We have demonstrated that, in vitro, TcPARP can ADP-ribosylate histones and AUK1 from this parasite, proteins that have been associated with both, cell cycle and DNA damage signaling.