Single nucleosome imaging reveals principles of transient multiscale chromatin reorganization triggered by histone ADP-ribosylation at DNA lesions
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 m...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61834-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849332573863411712 |
|---|---|
| author | Fabiola García Fernández Junwoo Park Catherine Chapuis Eva Pinto Jurado Victor Imburchia Rebecca Smith Edoardo José Longarini Angela Taddei Christian Hubert Nataliya Sokolovska Ivan Matić Sébastien Huet Judith Miné-Hattab |
| author_facet | Fabiola García Fernández Junwoo Park Catherine Chapuis Eva Pinto Jurado Victor Imburchia Rebecca Smith Edoardo José Longarini Angela Taddei Christian Hubert Nataliya Sokolovska Ivan Matić Sébastien Huet Judith Miné-Hattab |
| author_sort | Fabiola García Fernández |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e9c8eef5ac9c4889854b408ec5b4319c |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e9c8eef5ac9c4889854b408ec5b4319c2025-08-20T03:46:09ZengNature PortfolioNature Communications2041-17232025-07-0116111410.1038/s41467-025-61834-7Single nucleosome imaging reveals principles of transient multiscale chromatin reorganization triggered by histone ADP-ribosylation at DNA lesionsFabiola García Fernández0Junwoo Park1Catherine Chapuis2Eva Pinto Jurado3Victor Imburchia4Rebecca Smith5Edoardo José Longarini6Angela Taddei7Christian Hubert8Nataliya Sokolovska9Ivan Matić10Sébastien Huet11Judith Miné-Hattab12Laboratory of Computational,Quantitative and Synthetic Biology, CNRS, Institut de Biologie Paris-Seine, Sorbonne UniversitéLaboratory of Computational,Quantitative and Synthetic Biology, CNRS, Institut de Biologie Paris-Seine, Sorbonne UniversitéUniv Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes)-UMR 6290, BIOSIT-UMS 3480Univ Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes)-UMR 6290, BIOSIT-UMS 3480Univ Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes)-UMR 6290, BIOSIT-UMS 3480Univ Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes)-UMR 6290, BIOSIT-UMS 3480Doctoral School of Multidisciplinary Medical Sciences, University of SzegedInstitut Curie, Université PSL, Sorbonne University, CNRS, Nuclear DynamicsErrol laserLaboratory of Computational,Quantitative and Synthetic Biology, CNRS, Institut de Biologie Paris-Seine, Sorbonne UniversitéResearch Group of Proteomics and ADP-Ribosylation Signaling, Max Planck Institute for Biology of AgeingUniv Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes)-UMR 6290, BIOSIT-UMS 3480Laboratory of Computational,Quantitative and Synthetic Biology, CNRS, Institut de Biologie Paris-Seine, Sorbonne UniversitéAbstract 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.https://doi.org/10.1038/s41467-025-61834-7 |
| spellingShingle | Fabiola García Fernández Junwoo Park Catherine Chapuis Eva Pinto Jurado Victor Imburchia Rebecca Smith Edoardo José Longarini Angela Taddei Christian Hubert Nataliya Sokolovska Ivan Matić Sébastien Huet Judith Miné-Hattab Single nucleosome imaging reveals principles of transient multiscale chromatin reorganization triggered by histone ADP-ribosylation at DNA lesions Nature Communications |
| title | Single nucleosome imaging reveals principles of transient multiscale chromatin reorganization triggered by histone ADP-ribosylation at DNA lesions |
| title_full | Single nucleosome imaging reveals principles of transient multiscale chromatin reorganization triggered by histone ADP-ribosylation at DNA lesions |
| title_fullStr | Single nucleosome imaging reveals principles of transient multiscale chromatin reorganization triggered by histone ADP-ribosylation at DNA lesions |
| title_full_unstemmed | Single nucleosome imaging reveals principles of transient multiscale chromatin reorganization triggered by histone ADP-ribosylation at DNA lesions |
| title_short | Single nucleosome imaging reveals principles of transient multiscale chromatin reorganization triggered by histone ADP-ribosylation at DNA lesions |
| title_sort | single nucleosome imaging reveals principles of transient multiscale chromatin reorganization triggered by histone adp ribosylation at dna lesions |
| url | https://doi.org/10.1038/s41467-025-61834-7 |
| work_keys_str_mv | AT fabiolagarciafernandez singlenucleosomeimagingrevealsprinciplesoftransientmultiscalechromatinreorganizationtriggeredbyhistoneadpribosylationatdnalesions AT junwoopark singlenucleosomeimagingrevealsprinciplesoftransientmultiscalechromatinreorganizationtriggeredbyhistoneadpribosylationatdnalesions AT catherinechapuis singlenucleosomeimagingrevealsprinciplesoftransientmultiscalechromatinreorganizationtriggeredbyhistoneadpribosylationatdnalesions AT evapintojurado singlenucleosomeimagingrevealsprinciplesoftransientmultiscalechromatinreorganizationtriggeredbyhistoneadpribosylationatdnalesions AT victorimburchia singlenucleosomeimagingrevealsprinciplesoftransientmultiscalechromatinreorganizationtriggeredbyhistoneadpribosylationatdnalesions AT rebeccasmith singlenucleosomeimagingrevealsprinciplesoftransientmultiscalechromatinreorganizationtriggeredbyhistoneadpribosylationatdnalesions AT edoardojoselongarini singlenucleosomeimagingrevealsprinciplesoftransientmultiscalechromatinreorganizationtriggeredbyhistoneadpribosylationatdnalesions AT angelataddei singlenucleosomeimagingrevealsprinciplesoftransientmultiscalechromatinreorganizationtriggeredbyhistoneadpribosylationatdnalesions AT christianhubert singlenucleosomeimagingrevealsprinciplesoftransientmultiscalechromatinreorganizationtriggeredbyhistoneadpribosylationatdnalesions AT nataliyasokolovska singlenucleosomeimagingrevealsprinciplesoftransientmultiscalechromatinreorganizationtriggeredbyhistoneadpribosylationatdnalesions AT ivanmatic singlenucleosomeimagingrevealsprinciplesoftransientmultiscalechromatinreorganizationtriggeredbyhistoneadpribosylationatdnalesions AT sebastienhuet singlenucleosomeimagingrevealsprinciplesoftransientmultiscalechromatinreorganizationtriggeredbyhistoneadpribosylationatdnalesions AT judithminehattab singlenucleosomeimagingrevealsprinciplesoftransientmultiscalechromatinreorganizationtriggeredbyhistoneadpribosylationatdnalesions |