The wild-type p53 C-terminal domain mediates p53 interactions with poly-ADP-ribose polymerase 1 (PARP1) and poly-ADP-ribose (PAR) to facilitate p53-mediated DNA damage repair during DNA replication. However, oncogenic R273H mutant p53 (mtp53) C-terminal domain functions—and whether they contribute to R273H mtp53 oncogenesis—are not as well understood. In their study on page 1799, Lundine and colleagues assessed R273H mtp53 C-terminal domain deletion mutants in triple-negative breast cancer cells. The cover features a confocal microscopy image of a mtp53-PAR proximity ligation assay, where mtp53-PAR complexes fluoresce red and DAPI-stained nuclei fluoresce blue. The authors found that the R273H mtp53 C-terminal domain is critical for mtp53 interactions with PARP1 and PAR, and mediates DNA damage repair during DNA replication to facilitate cell cycle progression. This article is also Highlighted on page 1709.