Single-nucleosome imaging reveals principles of transient multiscale chromatin unfolding triggered by histone ADP-ribosylation at DNA lesions

GARCIA FERNANDEZ, F.; Chapuis, C.; PARK, J.; Pinto Jurado, E.; Imburchia, V.; Longarini, E. J.; Taddei, A.; Sokolovska, N.; Matic, I.; Huet, S.; Mine Hattab, J.

doi:10.1101/2024.08.28.610034

bioRxiv · 10.1101/2024.08.28.610034

Single-nucleosome imaging reveals principles of transient multiscale chromatin unfolding triggered by histone ADP-ribosylation at DNA lesions

GARCIA FERNANDEZ, F.·Chapuis, C.·PARK, J.·Pinto Jurado, E.·Imburchia, V.·Longarini, E. J.·Taddei, A.·Sokolovska, N.·Matic, I.·Huet, S.·Mine Hattab, J.

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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.

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GARCIA FERNANDEZ, F., Chapuis, C., PARK, J., Pinto Jurado, E., Imburchia, V., Longarini, E. J., Taddei, A., Sokolovska, N., Matic, I., Huet, S., Mine Hattab, J.. 2024-08-30. Single-nucleosome imaging reveals principles of transient multiscale chromatin unfolding triggered by histone ADP-ribosylation at DNA lesions. https://doi.org/10.1101/2024.08.28.610034

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