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Mol Biol Cell. 2016 Dec 1;27(24):3791-3799. Epub 2016 Oct 12.

The poly(ADP-ribose)-dependent chromatin remodeler Alc1 induces local chromatin relaxation upon DNA damage.

Author information

1
CNRS, UMR 6290, Institut Génétique et Développement de Rennes, 35043 Rennes, France.
2
Université de Rennes 1, Structure fédérative de recherche Biosit, 35043 Rennes, France.
3
Department of Physiological Chemistry, Biomedical Center Munich, Ludwig-Maximilians-Universität München, 82152 Planegg-Martinsried, Germany.
4
Department of Biology II, Ludwig-Maximilians-Universität München, 82152 Planegg-Martinsried, Germany.
5
Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry and Biochemistry, Ludwig-Maximilians-Universität München, 81377 Munich, Germany.
6
Munich Cluster for Systems Neurology (SyNergy), Biomedical Center Munich, Ludwig-Maximilians-Universität München, 81377 Munich, Germany.
7
Department of Physiological Chemistry, Biomedical Center Munich, Ludwig-Maximilians-Universität München, 82152 Planegg-Martinsried, Germany gyula.timinszky@med.lmu.de sebastien.huet@univ-rennes1.fr.
8
CNRS, UMR 6290, Institut Génétique et Développement de Rennes, 35043 Rennes, France gyula.timinszky@med.lmu.de sebastien.huet@univ-rennes1.fr.

Abstract

Chromatin relaxation is one of the earliest cellular responses to DNA damage. However, what determines these structural changes, including their ATP requirement, is not well understood. Using live-cell imaging and laser microirradiation to induce DNA lesions, we show that the local chromatin relaxation at DNA damage sites is regulated by PARP1 enzymatic activity. We also report that H1 is mobilized at DNA damage sites, but, since this mobilization is largely independent of poly(ADP-ribosyl)ation, it cannot solely explain the chromatin relaxation. Finally, we demonstrate the involvement of Alc1, a poly(ADP-ribose)- and ATP-dependent remodeler, in the chromatin-relaxation process. Deletion of Alc1 impairs chromatin relaxation after DNA damage, while its overexpression strongly enhances relaxation. Altogether our results identify Alc1 as an important player in the fast kinetics of the NAD+- and ATP-dependent chromatin relaxation upon DNA damage in vivo.

PMID:
27733626
PMCID:
PMC5170603
DOI:
10.1091/mbc.E16-05-0269
[Indexed for MEDLINE]
Free PMC Article

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