Abstract DNA damage in interphase leads to genome instability in part by promoting missegregation of chromosomes lacking centromeres. Yet the complete molecular mechanisms linking DNA damage to centromere dysfunction remain incompletely understood. Here, we show that prolonged exposure to genotoxic stress induces eviction of the histone H3 variant CENP-A. Displaced CENP-A relocalizes to nucleoli. This process depends on the DNA damage response kinase ATR and occurs in both human and mouse cells.
