caa a22 4500 606234977 CHVBK 20210128101240.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s11010-014-2205-1 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2205-1 Nuclear translocation of p19INK4d in response to oxidative DNA damage promotes chromatin relaxation [Elektronische Daten] [Silvina Sonzogni, María Ogara, Daniela Castillo, Pablo Sirkin, J. Radicella, Eduardo Cánepa] DNA is continuously exposed to damaging agents that can lead to changes in the genetic information with adverse consequences. Nonetheless, eukaryotic cells have mechanisms such as the DNA damage response (DDR) to prevent genomic instability. The DNA of eukaryotic cells is packaged into nucleosomes, which fold the genome into highly condensed chromatin, but relatively little is known about the role of chromatin accessibility in DNA repair. p19INK4d, a cyclin-dependent kinase inhibitor, plays an important role in cell cycle regulation and cellular DDR. Extensive data indicate that p19INK4d is a critical factor in the maintenance of genomic integrity and cell survival. p19INK4d is upregulated by various genotoxics, improving the repair efficiency for a variety of DNA lesions. The evidence of p19INK4d translocation into the nucleus and its low sequence specificity in its interaction with DNA prompted us to hypothesize that p19INK4d plays a role at an early stage of cellular DDR. In the present study, we demonstrate that upon oxidative DNA damage, p19INK4d strongly binds to and relaxes chromatin. Furthermore, in vitro accessibility assays show that DNA is more accessible to a restriction enzyme when a chromatinized plasmid is incubated in the presence of a protein extract with high levels of p19INK4d. Nuclear protein extracts from cells overexpressing p19INK4d are better able to repair a chromatinized and damaged plasmid. These observations support the notion that p19INK4d would act as a chromatin accessibility factor that allows the access of the repair machinery to the DNA damage site. Springer Science+Business Media New York, 2014 DNA damage response nationallicence Chromatin relaxation nationallicence p19INK4d nationallicence Genome integrity nationallicence INK4 : Inhibitor of cyclin-dependent kinase 4 nationallicence CDK : Cyclin-dependent kinase nationallicence MNase : Micrococcal nuclease nationallicence DDR : DNA damage response nationallicence OGG1 : 8-Oxoguanine DNA glycosylase 1 nationallicence Sonzogni Silvina Laboratorio de Biología Molecular, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria Pabellón II Piso 4, 1428, Buenos Aires, Argentina aut Ogara María Laboratorio de Biología Molecular, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria Pabellón II Piso 4, 1428, Buenos Aires, Argentina aut Castillo Daniela Laboratorio de Biología Molecular, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria Pabellón II Piso 4, 1428, Buenos Aires, Argentina aut Sirkin Pablo Laboratorio de Biología Molecular, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria Pabellón II Piso 4, 1428, Buenos Aires, Argentina aut Radicella J. CEA, Institute of Cellular and Molecular Radiobiology, 92265, Fontenay-aux-Roses, France aut Cánepa Eduardo Laboratorio de Biología Molecular, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria Pabellón II Piso 4, 1428, Buenos Aires, Argentina aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 398/1-2(2015-01-01), 63-72 0300-8177 398:1-2<63 2015 398 11010 https://doi.org/10.1007/s11010-014-2205-1 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2205-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sonzogni Silvina Laboratorio de Biología Molecular, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria Pabellón II Piso 4, 1428, Buenos Aires, Argentina aut NATIONALLICENCE 700 1- Ogara María Laboratorio de Biología Molecular, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria Pabellón II Piso 4, 1428, Buenos Aires, Argentina aut NATIONALLICENCE 700 1- Castillo Daniela Laboratorio de Biología Molecular, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria Pabellón II Piso 4, 1428, Buenos Aires, Argentina aut NATIONALLICENCE 700 1- Sirkin Pablo Laboratorio de Biología Molecular, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria Pabellón II Piso 4, 1428, Buenos Aires, Argentina aut NATIONALLICENCE 700 1- Radicella J. CEA, Institute of Cellular and Molecular Radiobiology, 92265, Fontenay-aux-Roses, France aut NATIONALLICENCE 700 1- Cánepa Eduardo Laboratorio de Biología Molecular, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria Pabellón II Piso 4, 1428, Buenos Aires, Argentina aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 398/1-2(2015-01-01), 63-72 0300-8177 398:1-2<63 2015 398 11010