Structural and Dynamical Signatures of Local DNA Damage in Live Cells*

The dynamic organization of chromatin inside the cell nucleus plays a key role in gene regulation and maintaining genome integrity. While the static folded state of the genome has been studied before, the dynamical signatures of processes such as transcription or DNA repair are unknown. We investigate the interphase chromatin dynamics in human cells in response to local damage, DNA double strand breaks (DSBs), by monitoring the DSB dynamics and the compaction of the surrounding chromatin in live cells. We find DSBs to possess a unique chromatin compaction profile, while being more mobile when located in the nuclear interior as opposed to the periphery. We show that DSB motion is subdiffusive, ATP-dependent, and exhibits unique dynamical signatures compared to undamaged chromatin. We find that DSB mobility follows a universal relationship based on the local environment suggesting that the repair processes are robust and likely deterministic. Such knowledge may help in detection of DNA damage in live cells and aid our biophysical understanding of genome integrity in health and disease [Eaton & Zidovska, Biophys. J., 2019].