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

Hafida Sellou (1, 2) , Théo Lebeaupin (1, 2) , Catherine Chapuis (1) , Rebecca Smith (2) , Anna Hegele (2) , Hari R. Singh (2) , Marek Kozlowski (2) , Sebastian Bultmann (3) , Andreas G. Ladurner (2) , Gyula Timinszky (2) , Sébastien Huet (1)

1 IGDR - Institut de Génétique et Développement de Rennes
2 Department of Physiological Chemistry
3 Department of Biology II - Neurobiology Biocenter

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.

Domaines: Organisation et fonctions cellulaires [q-bio.SC]

Hafida Sellou, Théo Lebeaupin, Catherine Chapuis, Rebecca Smith, Anna Hegele, et al.. The poly(ADP-ribose)-dependent chromatin remodeler Alc1 induces local chromatin relaxation upon DNA damage. Molecular Biology of the Cell, 2016, 27 (24), pp.3791-3799. ⟨10.1091/mbc.E16-05-0269⟩. ⟨hal-01382426⟩