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Abstract:

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 DNA-damage-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. © 2005 Nature Publishing Group. All rights reserved.

Registro:

Documento: Artículo
Título:Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells
Autor:Ceruti, J.M.; Scassa, M.E.; Flo, J.M.; Varone, C.L.; Cánepa, E.T.
Filiación:Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina
Palabras clave:Apoptosis; CDK4/6; DNA repair; INK4; Neuroblastoma; UV; caspase 3; DNA; DNA fragment; RNA; animal cell; apoptosis; article; cell cycle; cell strain BHK; chromatin structure; controlled study; DNA damage; DNA repair; DNA replication; DNA synthesis; enzyme activity; human; human cell; immunofluorescence; immunoprecipitation; neuroblastoma cell; nonhuman; Northern blotting; polyacrylamide gel electrophoresis; priority journal; protein expression; ultraviolet radiation; Western blotting; Animals; Apoptosis; Cell Cycle; Cell Cycle Proteins; Cell Line, Tumor; Cyclin-Dependent Kinase Inhibitor p19; DNA Damage; DNA Repair; DNA Replication; G1 Phase; Humans; Kinetics; Mice; Neuroblastoma; Protein Transport; RNA, Messenger; RNA, Neoplasm; Ultraviolet Rays
Año:2005
Volumen:24
Número:25
Página de inicio:4065
Página de fin:4080
DOI: http://dx.doi.org/10.1038/sj.onc.1208570
Título revista:Oncogene
Título revista abreviado:Oncogene
ISSN:09509232
CODEN:ONCNE
CAS:caspase 3, 169592-56-7; DNA, 9007-49-2; RNA, 63231-63-0; CDKN2D protein, human; Cdkn2d protein, mouse; Cell Cycle Proteins; Cyclin-Dependent Kinase Inhibitor p19; RNA, Messenger; RNA, Neoplasm
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_09509232_v24_n25_p4065_Ceruti.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09509232_v24_n25_p4065_Ceruti

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Citas:

---------- APA ----------
Ceruti, J.M., Scassa, M.E., Flo, J.M., Varone, C.L. & Cánepa, E.T. (2005) . Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells. Oncogene, 24(25), 4065-4080.
http://dx.doi.org/10.1038/sj.onc.1208570
---------- CHICAGO ----------
Ceruti, J.M., Scassa, M.E., Flo, J.M., Varone, C.L., Cánepa, E.T. "Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells" . Oncogene 24, no. 25 (2005) : 4065-4080.
http://dx.doi.org/10.1038/sj.onc.1208570
---------- MLA ----------
Ceruti, J.M., Scassa, M.E., Flo, J.M., Varone, C.L., Cánepa, E.T. "Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells" . Oncogene, vol. 24, no. 25, 2005, pp. 4065-4080.
http://dx.doi.org/10.1038/sj.onc.1208570
---------- VANCOUVER ----------
Ceruti, J.M., Scassa, M.E., Flo, J.M., Varone, C.L., Cánepa, E.T. Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells. Oncogene. 2005;24(25):4065-4080.
http://dx.doi.org/10.1038/sj.onc.1208570