p53-binding protein 1 (53BP1) is a key component of the non-homologous end joining (NHEJ) DNA repair pathway, which is active throughout interphase. 53BP1 is known to cluster (with nuclear factors) to form nuclear bodies (NBs) at sites of unresolved DNA lesions generated during S phase, which are transmitted through mitosis; these NBs are thought to shield broken DNA ends from nucleolytic digestion. In this study (Bleiler et al., 2023), Charles Giardina and colleagues identify a new type of 53BP1 NB, mitotic stress bodies (MSBs), that form in cancer cell lines in response to delayed mitosis. Like other 53BP1 NBs, MSBs form liquid-liquid phase-separated particles but differ owing to the presence of lamin A/C and the DNA repair protein RIF1. The authors characterise these bodies, showing that they reside close to centromeres but move away from chromatin (and decrease in number) after cells are released from mitotic arrest. Furthermore, the oligomerization domain region of 53BP1, but not the N-terminal or Tudor domain (TD), is required and sufficient for MSB formation. Interestingly, MSBs are found spontaneously in dividing cancer cell lines but not in non-transformed cells. Thus, MSBs might facilitate the survival of cancer cells by sequestering 53BP1, which can induce apoptotic signalling when it accumulates. In conclusion, this study highlights the existence of MSBs as a novel 53BP1 NB that might be employed by cancer cells to promote cell survival following aberrant mitoses.
