**4. Conclusion**

Thanks to recent advanced in fast and high-resolution microscopy, it became possible to quantify chromatin mobility with unprecedented precision and to understand how chromatin explores the nuclear space. Following DSBs, chromatin mobility is dramatically altered in budding yeast both at the site of DNA damage and genome wide. In mammalian cells, DSBs mobility is strongly influenced by cell cycle stage, chromatin state, and repair pathway choice. For example, while DSBs induced in pericentric heterochromatin during the S and G2 phases of the cell cycle are more mobile and relocate to the nuclear periphery, DSBs generated during the G1 phase remain stable. Changes of chromatin mobility upon DNA damage is an intriguing phenomenon, and over the last five years, several views to explain it have been proposed in the literature. They can be grouped into two classes: (1) increase in chromatin motion is due to intrinsic chromatin modifications which require chromatin remodelers, kinases, and repair proteins involved in the DNA response machinery; (2) increase in chromatin motion due to changes of external mechanical constraints that maintain chromatin and to the action of molecular motors. It is likely that both mechanisms act in concert to drive differently damaged chromatin depending on the type of damages, the chromatin state, or the cell cycle.

Several questions remain open: how changes in chromatin dynamics alter its organization at the scale of TADs? Is there a global change in mechanical properties of the chromatin upon DSBs, such as an increase in chromatin rigidity? In the future, it will be an exciting challenge to investigate changes in chromatin organization and dynamics upon DNA damage combining different approaches from live cell microscopy, super resolution imaging, and Hi-C.
