INVESTIGADORES
PREGI Nicolas
congresos y reuniones científicas
Título:
Transcriptional regulation of E2F factors in DNA damage response.
Autor/es:
CASTILLO, DS; OGARA, MF; CÁNEPA, ET; PREGI, N
Lugar:
San Miguel de Tucumán, Tucumán, Argentina
Reunión:
Congreso; XLV Reunión Científica Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2009
Institución organizadora:
Sociedad Argentina de Investigación en Bioquímica y Biología Molecular
Resumen:
Following genotoxic stress, the E2F1 transcription factor
has been shown to
undergo post-translational modifications that correlate with a
stabilization and increase in its protein levels. The aim of this work is to examine whether this
increase in protein levels is only due to its gained stability or is
also a result of enhanced transcription of the E2F1 gene. This study also includes the other family members, E2F2 to E2F5.
We subjected HEK293 and HN9 cells to genotoxic stress -such as UV, H2O2 and neocarzinostatin- and allowed them to
trigger a DNA repair response and recover for different
time periods. Northern Blot analyses were carried out using E2F1 to E2F5 probes. Quantifications revealed
that E2F1 mRNA levels were induced between 4 to 8 hours following genotoxic exposition in both cell lines for all types of stress, reaching a 3 to 4.5-fold increase in HEK293 and a 2 to 3.5-fold increase in HN9 cells. Surprisingly, E2F2
transcription was enhanced 2.5 to 4-fold from 4 to 12 hours of recovery
only in neuronal HN9 cells after every stress. E2F3,
E2F4 and
E2F5
mRNA levels remained unchanged. Preliminary results suggest that MAPK and
ATM/ATR pathways are involved in this response.
Our
results reveal a new mechanism in which E2F1 and E2F2 respond to genotoxic
stress by
increasing their transcript levels.