INVESTIGADORES
CANEPA Eduardo Tomas
congresos y reuniones científicas
Título:
E2F1 AND E2F2 CONTRIBUTE TO THE DNA DAMAGE RESPONSE IN NEURONAL CELLS
Autor/es:
DANIELA S. CASTILLO; MARÍA F. OGARA; EDUARDO T. CÁNEPA; NICOLÁS PREGI
Lugar:
Potrero de los Funes
Reunión:
Congreso; XLVII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2011
Institución organizadora:
Sociedad Argentina de Investigación en Bioquímica y Biología Molecular
Resumen:
The E2F transciption factors are key regulators of multiple cellular
processes including proliferation, development and apoptosis. In
the last years, E2F1 has been described to participate in the DNA
damage response, an event that requires its post-translational
modification and subsequent protein stabilization. We have
previously reported that the E2F1 and E2F2 genes are also
regulated at the transcriptional level and become induced
following different genotoxic stimuli (neocarzinostatin, H2O2 and
UV) in human and murine neuronal cells. Consistently, here we
show that DNA damage increased E2F transcriptional activity 4-
fold, as assessed by reporter assays. Our goal was to characterize
and evaluate the significance of E2F1 and E2F2 induction in the
maintenance of genome integrity. Inhibition of the MAPK and
ATM/ATR pathways prevented the upregulation of E2F1 and E2F2
mRNA levels in response to genotoxic stress. E2F1 and E2F2
ablation using antisense oligonucleotides resulted in increased
levels of gH2AX following DNA damage, as observed by
immunofluorescence microscopy. Moreover, clonogenic assays
showed that cells with reduced E2F1 and E2F2 mRNA levels have
33% and 59% diminished proliferative capacity after genotoxic
stimuli, respectively.
Our results suggest that the enhanced transcription of E2F1 and
E2F2 plays a relevant role during the DNA damage response.gH2AX following DNA damage, as observed by
immunofluorescence microscopy. Moreover, clonogenic assays
showed that cells with reduced E2F1 and E2F2 mRNA levels have
33% and 59% diminished proliferative capacity after genotoxic
stimuli, respectively.
Our results suggest that the enhanced transcription of E2F1 and
E2F2 plays a relevant role during the DNA damage response.