INVESTIGADORES
CERUTI Julieta Maria
artículos
Título:
Induction of p19INK4d in response to ultraviolet light improves DNA repair
Autor/es:
JULIETA M CERUTI; MARÍA E SCASSA; JUAN M FLO; CECILIA L VARONE; EDUARDO T CÁNEPA
Revista:
ONCOGENE
Editorial:
nature publishing group
Referencias:
Año: 2005 vol. 24 p. 4065 - 4080
ISSN:
0950-9232
Resumen:
The genetic instability driving tumorigenesis is fuelled by
DNA damage and by errors made by the DNA replication.
Upon DNA damage the cell organizes an integrated
response not only by the classical DNA repair mechanisms
but also involving mechanisms of replication, transcription,
chromatin structure dynamics, cell cycle progression,
and apoptosis. In the present study, we investigated the
role of p19INK4d in the response driven by neuroblastoma
cells against DNA injury caused by UV irradiation. We
show that p19INK4d is the only INK4 protein whose
expression is induced by UV light in neuroblastoma cells.
Furthermore, p19INK4d translocation from cytoplasm to
nucleus is observed after UV irradiation. Ectopic expression
of p19INK4d clearly reduces the UV-induced
apoptosis as well as enhances the cellular ability to repair
the damaged DNA. It is clearly shown that DNA repair is
the main target of p19INK4d effect and that diminished
apoptosis is a downstream event. Importantly, experiments
performed with CDK4 mutants suggest that these
p19INK4d effects would be independent of its role as a cell
cycle checkpoint gene. The results presented herein
uncover a new role of p19INK4d as regulator of DNAdamage-
induced apoptosis and suggest that it protects
cells from undergoing apoptosis by allowing a more
efficient DNA repair. We propose that, in addition to its
role as cell cycle inhibitor, p19INK4d is involved in
maintenance of DNA integrity and, therefore, would
contribute to cancer prevention.