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.