Garcia, Fernandez Fabiola and Park, Junwoo and Chapuis, Catherine and Pinto, Eva and Imburchia, Victor and Smith, Rebecca and Jose, Longarini Edoardo and Taddei, Angela and Hubert, Christian and Sokolovska, Nataliya and Matic, Ivan and Huet, Sebastien and Mine-Hattab, Judith (2025) Single nucleosome imaging reveals principles of transient multiscale chromatin reorganization triggered by histone ADP-ribosylation at DNA lesions. NATURE COMMUNICATIONS, 16 (1). No. -6652. ISSN 2041-1723
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Abstract
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. © 2025. The Author(s).
| Item Type: | Article |
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| Additional Information: | Funding Agency and Grant Number: French National Research Agency [ANR-24-INBS-0005 FBI BIOGEN]; Agence Nationale de la Recherche [ANR-18-CE12-0015-03, ANR-22-CE12-0039]; Idex Sorbonne University Alliance; IBPS Incentive Action; ATIP Avenir; Max Planck Society; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy (CECAD) [EXC 2030-390661388]; European Research Council [ERC-CoG-864117]; EMBO Young Investigator Program; Cologne Graduate School of Ageing Research Funding text: We thank C. Maison, D. Bailly, A. Forest (Institut Curie), and C. Fouquet (Institut de Biologie Paris Seine, Sorbonne University) for their help with the cell culture. The authors also thank the PICT-IBiSA@Pasteur Imaging Facility of the Institut Curie, a member of the France Bioimaging National Infrastructure (ANR-24-INBS-0005 FBI BIOGEN), C. Chaumeton, and F. Lam from the cellular Imaging Facility (Institut de Biologie Paris Seine, Sorbonne Universite). We thank the Microscopy-Rennes Imaging Center (BIOSIT, Universite de Rennes), member of the national infrastructure France-BioImaging supported by the French National Research Agency (ANR-24-INBS-0005 FBI BIOGEN), for providing access to the imaging setups, as well as S. Dutertre, X. Pinson, and G. Le Marchand for technical assistance on the microscopes. We thank J. Morris, G. Timinszky, J. Ellenberg, S. Buratowski, A. Coulon, and L. Lavis for sharing reagents. We are grateful to E. Fabre for her fruitful comments on the manuscript and A. Mansuy for sharing his software expertise. Illustrations in figures were created in BioRender. Garcia Fernandez, F. (2025) https://BioRender.com/5akfy1x. The S.H.'s and J.M.H.'s groups received financial support from the Agence Nationale de la Recherche (ANR-18-CE12-0015-03 RepairChrom and ANR-22-CE12-0039 AROSE). The J.M-H team was financially supported by the i-Bio Initiative from the Idex Sorbonne University Alliance, the IBPS Incentive Action and the ATIP Avenir 2021. I.M.'s lab was funded by the Max Planck Society, the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy (CECAD, EXC 2030-390661388) and by the European Research Council (ERC-CoG-864117). I.M. and E.J.L. received support from the EMBO Young Investigator Program and the Cologne Graduate School of Ageing Research, respectively. This work has inspired part of the Muse-IC project, a collaborative project between musicians and composers aiming to create musical pieces inspired by recent scientific discoveries. |
| Subjects: | Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3011 Biochemistry / biokémia Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3015 Molecular biology / molekuláris biológia Q Science / természettudomány > QR Microbiology / mikrobiológia |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 10 Feb 2026 13:51 |
| Last Modified: | 10 Feb 2026 13:51 |
| URI: | https://real.mtak.hu/id/eprint/233681 |
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