INVESTIGADORES
CERUTI Julieta Maria
congresos y reuniones científicas
Título:
CDK4/6 INHIBITOR p19INK4d INCREASES THE DNA REPAIR ABILITY IN FIBROBLASTS.
Autor/es:
CÁNEPA, EDUARDO; JULIO, MIGUEL; CERUTI, JULIETA; CARCAGNO, ABEL; GUBERMAN, ALEJANDRA; SCASSA, MARÍA
Lugar:
Bariloche, Argentina.
Reunión:
Congreso; XXXIX Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2003
Institución organizadora:
SAIB
Resumen:
The four proteins of the INK4 family posses a similar structure
and bind to CDK4/6 with similar affinity driving to a G1 cell
cycle arrest, but they are reported to have different biological roles.
The aim of this work was to evaluate if p19INK4d induces a second
photoprotective response after DNA damage. Northern blot analysis
show that p19 is up-regulated after UV irradiation in BHK cells.
Levels of p19INK4d mRNA peaked 12 h after UV treatment. This
induction resulted dose dependent and started at 5 mJ/cm2. The
apparent p19 mRNA half life was 3 h in irradiated and non
irradiated cells. The same behavior was observed when the protein
half-life was estimated in 2,5 h by pull-chase assays with 35S-met.
Nuclear run-on experiments revealed an appreciable increase in
the rate of p19 mRNA synthesis in UV treated cells in comparison
with untreated ones. We measured DNA repair capacity by host
cell reactivation assay. The overexpression of p19 resulted in a
80% increased repair of UV-induced DNA damage while the
antisense version drove a diminished expression of DNA tested.
Nevertheless, mimosine (an inhibitor of G1/S phase progression)
or overexpression of p16INK4a displayed a minor effect on the rate
of repair as assessed by HCR, suggesting that p19INK4d exerts its
action independently from cell cycle arrest. Regardless of p19INK4dINK4d induces a second
photoprotective response after DNA damage. Northern blot analysis
show that p19 is up-regulated after UV irradiation in BHK cells.
Levels of p19INK4d mRNA peaked 12 h after UV treatment. This
induction resulted dose dependent and started at 5 mJ/cm2. The
apparent p19 mRNA half life was 3 h in irradiated and non
irradiated cells. The same behavior was observed when the protein
half-life was estimated in 2,5 h by pull-chase assays with 35S-met.
Nuclear run-on experiments revealed an appreciable increase in
the rate of p19 mRNA synthesis in UV treated cells in comparison
with untreated ones. We measured DNA repair capacity by host
cell reactivation assay. The overexpression of p19 resulted in a
80% increased repair of UV-induced DNA damage while the
antisense version drove a diminished expression of DNA tested.
Nevertheless, mimosine (an inhibitor of G1/S phase progression)
or overexpression of p16INK4a displayed a minor effect on the rate
of repair as assessed by HCR, suggesting that p19INK4d exerts its
action independently from cell cycle arrest. Regardless of p19INK4dINK4d mRNA peaked 12 h after UV treatment. This
induction resulted dose dependent and started at 5 mJ/cm2. The
apparent p19 mRNA half life was 3 h in irradiated and non
irradiated cells. The same behavior was observed when the protein
half-life was estimated in 2,5 h by pull-chase assays with 35S-met.
Nuclear run-on experiments revealed an appreciable increase in
the rate of p19 mRNA synthesis in UV treated cells in comparison
with untreated ones. We measured DNA repair capacity by host
cell reactivation assay. The overexpression of p19 resulted in a
80% increased repair of UV-induced DNA damage while the
antisense version drove a diminished expression of DNA tested.
Nevertheless, mimosine (an inhibitor of G1/S phase progression)
or overexpression of p16INK4a displayed a minor effect on the rate
of repair as assessed by HCR, suggesting that p19INK4d exerts its
action independently from cell cycle arrest. Regardless of p19INK4d2. The
apparent p19 mRNA half life was 3 h in irradiated and non
irradiated cells. The same behavior was observed when the protein
half-life was estimated in 2,5 h by pull-chase assays with 35S-met.
Nuclear run-on experiments revealed an appreciable increase in
the rate of p19 mRNA synthesis in UV treated cells in comparison
with untreated ones. We measured DNA repair capacity by host
cell reactivation assay. The overexpression of p19 resulted in a
80% increased repair of UV-induced DNA damage while the
antisense version drove a diminished expression of DNA tested.
Nevertheless, mimosine (an inhibitor of G1/S phase progression)
or overexpression of p16INK4a displayed a minor effect on the rate
of repair as assessed by HCR, suggesting that p19INK4d exerts its
action independently from cell cycle arrest. Regardless of p19INK4d35S-met.
Nuclear run-on experiments revealed an appreciable increase in
the rate of p19 mRNA synthesis in UV treated cells in comparison
with untreated ones. We measured DNA repair capacity by host
cell reactivation assay. The overexpression of p19 resulted in a
80% increased repair of UV-induced DNA damage while the
antisense version drove a diminished expression of DNA tested.
Nevertheless, mimosine (an inhibitor of G1/S phase progression)
or overexpression of p16INK4a displayed a minor effect on the rate
of repair as assessed by HCR, suggesting that p19INK4d exerts its
action independently from cell cycle arrest. Regardless of p19INK4dINK4a displayed a minor effect on the rate
of repair as assessed by HCR, suggesting that p19INK4d exerts its
action independently from cell cycle arrest. Regardless of p19INK4dINK4d exerts its
action independently from cell cycle arrest. Regardless of p19INK4dINK4d
precise mechanism the present data demonstrate that this protein
is not only associated with cell cycle arrest but also with
enhancement of DNA repair.