INGEBI   02650
INSTITUTO DE INVESTIGACIONES EN INGENIERIA GENETICA Y BIOLOGIA MOLECULAR "DR. HECTOR N TORRES"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
UNUSUAL LOCALIZATION OF POLY(ADP-RIBOSE) METABOLISM-RELATED ENZYMES IN TRYPANOSOMATIDS
Autor/es:
SCHLESINGER M; KEVORKIAN ML; VILCHEZ LARREA SC; FLAWIÁ MM; FERNÁNDEZ VILLAMIL SH
Lugar:
Rosario
Reunión:
Congreso; 50th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2014
Institución organizadora:
Sociedad Argentina de Investigación en Bioquimica y Biología Molecular
Resumen:
Poly(ADP-ribose) polymerase (PARP) and poly(ADP-ribose) glycohydrolase (PARG) are responsible for poly(ADPribose) polymer (PAR) metabolism and have been previously reported in trypanosomatids by our group. We investigated the localization of both enzymes in T.cruzi and T.brucei and, interestingly, PARP was localized mostly in the cytoplasm, whereas after oxidative stress (OS), PARP translocated to the nucleus. However, PARG was always nuclear. These localizations are opposite to what has been described in other organisms. In accordance, PAR formation was detected in the nuclei of the cells after OS. To date, neither potential nuclear localization signals nor other putative sequences involved in the protein targeting to different subcellular compartments in these parasites have been ascertained. By using parasites overexpressing the full length PARP and different PARP domains tagged to eYFP or HA, we demonstrate that the N-terminal region is crucial for PARP nuclear localization, even in the absence of OS. This data also implies that nuclear PAR metabolism may be regulated by the nucleus-cytoplasm shuttling of the only PARP. This particular localization of PARP in kynetoplastids could be related to the maintenance of the integrity of kinetoplast DNA (kDNA), essential for these parasites and could be a strategy to alternatively deliver the protein to this organelle or to the nucleus.