Temporal and spatial dynamics of DNA double-strand break repair centers

Over the past two decades, there has been intense debate regarding whether DNA double-strand breaks (DSBs) maintain a relatively stable position or cluster in mammalian cells. The clustering of DSB and its spatiotemporal properties remain unclear. Here, we provided evidence supporting DSB clustering, using laser microirradiation to induce high-precision damage in cells. The probability of 53BP1 foci clustering varies with the distance between them. 53BP1 foci clustering occurs during the early phase of DNA damage response (DDR) and the repair phase, but not during the repair plateau phase. The clustering at different phases has distinct implications for DNA repair. Clustering accelerates the DSB repair process. These results demonstrate that the extent of 53BP1 foci clustering is influenced by both temporal and spatial factors. Such findings could enhance our understanding of the mechanism of DSB clustering and the DDR, ultimately contributing to the development of improved DNA repair therapies for various diseases.

Biophysics; DNA repair; DSB clustering.