Single nucleosome imaging reveals principles of transient multiscale chromatin reorganization triggered by histone ADP-ribosylation at DNA lesions
Timely access to DNA lesions is crucial for genome integrity. This process requires profound remodeling of densely packed chromatin to establish a repair-competent architecture. However, limited resolution has made it impossible to fully understand these remodeling events. Here, combining microirradiation with live-cell multiscale imaging, we report that DNA damage-induced changes in genome packing rely on the conformational behaviour of the chromatin fiber. Immediately after damage, a transient increase in nucleosome mobility switches chromatin from a densely-packed state to a looser conformation, making it accessible to repair. While histone poly-ADP-ribosylation is required to trigger this switch, mono-ADP-ribosylation is sufficient to maintain the open-chromatin state. The removal of these histone marks by the ARH3 hydrolase then leads to chromatin recondensation. Together, our multiscale study of chromatin dynamics establishes a global model: distinct waves of histone ADP-ribosylation control nucleosome mobility, triggering a transient breathing of chromatin, crucial for initiating the DNA damage response.
Authors
- Rebecca Smith (ORCID: https://orcid.org/0000-0002-1658-5635)
- Junwoo Park (ORCID: https://orcid.org/0009-0004-4346-2472)
- Catherine Chapuis (ORCID: https://orcid.org/0000-0002-3765-0969)
- Judith Miné-Hattab (ORCID: https://orcid.org/0000-0001-9986-4092)
- Edoardo José Longarini (ORCID: https://orcid.org/0000-0003-3919-1169)
- Nataliya Sokolovska (ORCID: https://orcid.org/0000-0001-8841-1725)
- Fabiola García Fernández (ORCID: https://orcid.org/0000-0003-2909-236X)
- Ivan Matić (ORCID: https://orcid.org/0000-0003-0170-7991)
- Angela Taddei (ORCID: https://orcid.org/0000-0002-3217-0739)
- Sébastien Huet (ORCID: https://orcid.org/0000-0002-3978-0003)
- Christian Hubert (ORCID: https://orcid.org/0000-0001-6525-1845)
- Eva Pinto Jurado
- Victor Imburchia (ORCID: https://orcid.org/0009-0008-5107-0419)
Institutions
- Centre National de la Recherche Scientifique (FR)
- University of Cologne (DE)
- Princeton University (US)
- University of Szeged (HU)
- Université Paris Sciences et Lettres (FR)
- HUN-REN Szegedi Biológiai Kutatóközpont (HU)
- Sorbonne Université (FR)
- Biologie Computationnelle, Quantitative et Synthétique (FR)
- Institut de Biologie Paris-Seine (FR)
- Alpes Lasers (Switzerland) (CH)
- Institut de génétique et de développement de Rennes (FR)
- Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE)
- Dynamique du noyau (FR)
- Max Planck Institute for Biology of Ageing (DE)
- Institute of Genetics (HU)
- Hungarian Research Network (HU)
- Université de Rennes (FR)
- Institut Curie (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-07-19
- DOI
- https://doi.org/10.1038/s41467-025-61834-7
- Citations
- 4
- Primary Topic
- PARP inhibition in cancer therapy
- Type
- article
- Field-Weighted Citation Impact
- 4.18
Funders
- Biogen
- Infrastructures en Biologie Santé et Agronomie
- Deutsche Forschungsgemeinschaft
- Agence Nationale de la Recherche
- Max-Planck-Gesellschaft
- Sorbonne Université