De Novo Centromere Formation: One's Company, Two's a Crowd

Chromosomes containing two centromeres (dicentrics) trigger chromosome instability that is avoided by the enigmatic process of centromere inactivation. In this issue of Developmental Cell, Palladino et al. (2020) combine in vivo chromosome engineering and Drosophila genetics to assess consequences of de novo centromere formation and clarify models of centromere inactivation.