Chromatin relaxation-mediated induction of p19INK4d increases the ability of cells to repair damaged DNA

Autor: Pablo Federico Sirkin, Mariela C. Marazita, Silvina Veronica Sonzogni, Maria Florencia Ogara, Abel L. Carcagno, Julieta M. Ceruti, Eduardo T. Cánepa
Jazyk: angličtina
Rok vydání: 2013
Předmět:
DNA Repair
Gene Expression
lcsh:Medicine
Cell Cycle Proteins
Ataxia Telangiectasia Mutated Proteins
Genotoxic Stress
Biochemistry
purl.org/becyt/ford/1 [https]
Molecular cell biology
p19INK4d
Signaling in Cellular Processes
lcsh:Science
Cellular Stress Responses
Multidisciplinary
Chromosome Biology
Physics
Chloroquine
Genomics
Bioquímica y Biología Molecular
Chromatin
Cell biology
DNA-Binding Proteins
Nucleic acids
Epigenetics
CIENCIAS NATURALES Y EXACTAS
Signal Transduction
Research Article
DNA re-replication
Ultraviolet Rays
DNA damage
DNA repair
Biophysics
Protein Serine-Threonine Kinases
Biology
Cell cycle
Models
Biological
Chromatin remodeling
Cell Line
Ciencias Biológicas
Genetics
Humans
CHEK1
Cyclin-Dependent Kinase Inhibitor p19
purl.org/becyt/ford/1.6 [https]
Tumor Suppressor Proteins
lcsh:R
DNA
G2-M DNA damage checkpoint
Molecular biology
Checkpoint Kinase 2
Checkpoint Kinase 1
lcsh:Q
Transcriptional Signaling
Protein Kinases
E2F1 Transcription Factor
DNA Damage
Mutagens
Zdroj: PLoS ONE, Vol 8, Iss 4, p e61143 (2013)
CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET
PLoS ONE
ISSN: 1932-6203
Popis: The maintenance of genomic integrity is of main importance to the survival and health of organisms which are continuously exposed to genotoxic stress. Cells respond to DNA damage by activating survival pathways consisting of cell cycle checkpoints and repair mechanisms. However, the signal that triggers the DNA damage response is not necessarily a direct detection of the primary DNA lesion. In fact, chromatin defects may serve as initiating signals to activate those mechanisms. If the modulation of chromatin structure could initiate a checkpoint response in a direct manner, this supposes the existence of specific chromatin sensors. p19INK4d, a member of the INK4 cell cycle inhibitors, plays a crucial role in regulating genomic stability and cell viability by enhancing DNA repair. Its expression is induced in cells injured by one of several genotoxic treatments like cis-platin, UV light or neocarzinostatin. Nevertheless, when exogenous DNA damaged molecules are introduced into the cell, this induction is not observed. Here, we show that p19INK4d is enhanced after chromatin relaxation even in the absence of DNA damage. This induction was shown to depend upon ATM/ATR, Chk1/Chk2 and E2F activity, as is the case of p19INK4d induction by endogenous DNA damage. Interestingly, p19INK4d improves DNA repair when the genotoxic damage is caused in a relaxed-chromatin context. These results suggest that changes in chromatin structure, and not DNA damage itself, is the actual trigger of p19INK4d induction. We propose that, in addition to its role as a cell cycle inhibitor, p19INK4d could participate in a signaling network directed to detecting and eventually responding to chromatin anomalies. Fil: Ogara, Maria Florencia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Sirkin, Pablo Federico. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Carcagno, Abel Luis. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Marazita, Mariela Claudia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Sonzogni, Silvina Veronica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Ceruti, Julieta María. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Canepa, Eduardo Tomas. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Databáze: OpenAIRE
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