To protect themselves, cells need to distinguish exogenous DNA such as viral DNA from their own. How is this achieved? Interestingly, exogenous DNA can be eliminated during mitosis by confining it to only one daughter cell (for example, see Denoth-Lippuner et al.). By contrast, the mitotic segregation of chromosomes is symmetric owing to the centromere that they carry. This difference led Kruitwagen et al. to hypothesize that the centromere is the defining mark of self-DNA. Do centromeres have this capacity solely owing to their spindle attachment function, or by additional means?

Such plasmids are not attached to nuclear pore complexes (NPCs) during mitosis (Denoth-Lippuner et al.). However, centromere removal prevented these plasmids from condensing, and they attached to the NPCs. Indeed, during mitosis, the plasmids asymmetrically segregate with the NPCs to only one daughter cell. Thus, Kruitwagen et al. proposed that only centromeric DNA is recognized as self, condensed, symmetrically partitioned by the spindle machinery and stably maintained in dividing cells. By contrast, exogenous DNA molecules that lack centromeres ‘qualify’ as non-self-DNA, are confined to one cell and are rapidly lost from the cell population.