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Abstract
Translocations, which occur when two DNA DSBs are abnormally rejoined, are highly deleterious genome rearrangements favoring cancer initiation and progression. However, the mechanisms that drive their formation remain poorly understood. One prerequisite for translocation is the juxtaposition of two distant DSBs, an event that would be favored if DSBs cluster, i.e. are brought together in spatial proximity within the nucleus. In budding yeast, a lacO- or TetO-tagged genomic locus exhibits increased motion when it is damaged with the I-SceI endonuclease. Intriguingly, this phenomenon, referred to as local mobility, is accompanied by a global mobility process whereby the other chromosomes also explore wider volumes in the nuclear space, although to a lesser extent than the damaged locus itself13. Moreover, induction of two DSBs by the HO and I-SceI endonucleases triggers formation of a single Rad52 focus, thus suggesting that DSBs can indeed coalesce in yeast.