Single nucleosome imaging reveals principles of transient multiscale chromatin reorganization triggered by histone ADP-ribosylation at DNA lesions.
Résumé
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.
Domaines
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Cite 10.5281/zenodo.13334706 Ouvrage Park, J. (2025). HTC (Version v1.0.8). Zenodo. https://doi.org/10.5281/ZENODO.13334706
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Cite 10.6084/m9.figshare.28458161 Jeu de données GARCIA FERNANDEZ, F. N. (2025). Single-nucleosome imaging reveals principles of transient multiscale chromatin reorganization triggered by histone ADP-ribosylation at DNA lesions [Data set]. figshare. https://doi.org/10.6084/M9.FIGSHARE.28458161