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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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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1768544234750607360 |