Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells

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...

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Autores principales: Ceruti, Julieta María, Scassa, María Elida, Varone, Cecilia Laura, Cánepa, Eduardo Tomás
Publicado: 2005
Materias:
UV
DNA
RNA
Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09509232_v24_n25_p4065_Ceruti
http://hdl.handle.net/20.500.12110/paper_09509232_v24_n25_p4065_Ceruti
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spelling paper:paper_09509232_v24_n25_p4065_Ceruti2023-06-08T15:54:49Z Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells Ceruti, Julieta María Scassa, María Elida Varone, Cecilia Laura Cánepa, Eduardo Tomás 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 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. Fil:Ceruti, J.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Scassa, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Varone, C.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Cánepa, E.T. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2005 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09509232_v24_n25_p4065_Ceruti http://hdl.handle.net/20.500.12110/paper_09509232_v24_n25_p4065_Ceruti
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic 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
spellingShingle 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
Ceruti, Julieta María
Scassa, María Elida
Varone, Cecilia Laura
Cánepa, Eduardo Tomás
Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells
topic_facet 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
description 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.
author Ceruti, Julieta María
Scassa, María Elida
Varone, Cecilia Laura
Cánepa, Eduardo Tomás
author_facet Ceruti, Julieta María
Scassa, María Elida
Varone, Cecilia Laura
Cánepa, Eduardo Tomás
author_sort Ceruti, Julieta María
title Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells
title_short Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells
title_full Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells
title_fullStr Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells
title_full_unstemmed Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells
title_sort induction of p19ink4d in response to ultraviolet light improves dna repair and confers resistance to apoptosis in neuroblastoma cells
publishDate 2005
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09509232_v24_n25_p4065_Ceruti
http://hdl.handle.net/20.500.12110/paper_09509232_v24_n25_p4065_Ceruti
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