Organizing DNA repair in the nucleus: DSBs hit the road

•DSB triggers intra-TAD chromatin changes.•DSBs move within the nuclear space.•Motion depends on the genomic position of the DSB and on its ease to be repaired.•Mobility ensures homology search, DSB clustering and positioning within the nucleus.

In the past decade, large-scale movements of DNA double strand breaks (DSBs) have repeatedly been identified following DNA damage. These mobility events include clustering, anchoring or peripheral movement at subnuclear structures. Recent work suggests roles for motion in homology search and in break sequestration to preclude deleterious outcomes. Yet, the precise functions of these movements still remain relatively obscure, and the same holds true for the determinants. Here we review recent advances in this exciting area of research, and highlight that a recurrent characteristic of mobile DSBs may lie in their inability to undergo rapid repair. A major future challenge remains to understand how DSB mobility impacts on genome integrity.