Faithful maintenance of the genome is essential for preventing cancer and hereditary disease. DNA double strand breaks pose the greatest challenge to this fidelity, requiring repair machinery to organize at specific nuclear locations, persist for hours, and dissolve completely when repair is finished. Passive thermodynamics predicts progressive coarsening of repair material, where fewer, larger foci grow at the expense of smaller ones, leaving some breaks without sufficient repair machinery. How this spatial organization is actively regulated in cells to maintain effective repair remains unknown.

Using quantitative single-cell imaging, we find that p53, canonically understood to be a transcription factor, accumulates at DNA breaks in a time-dependent manner controlled by post-translational modifications at p53's C-terminus. From these results, we hypothesize that p53 limits repair focus growth through competition with the repair scaffold’s chromatin binding, an interaction that could regulate focus size and prevent coarsening. These results suggest that p53's role in genome maintenance extends beyond transcription to the direct physical organization of repair machinery at break sites.