To investigate the mother-daughter segregation bias of plasmids, we used live-cell imaging to follow the behavior of extrachromosomal DNA. We show that both an excised DNA ring and a centromere-deficient ARS plasmid move freely in the nucleoplasm yet show a strong segregation bias for the mother cell. Computational modeling shows that the geometrical shape of the dividing yeast nucleus and length of mitosis severely restrict the passive diffusion of episomes into daughter nuclei. Predictions based on simulated nuclear division were tested with mutants that extend the length of mitosis. Finally, explaining how various anchors can improve mitotic segregation, we show that plasmid partitioning is improved by tethering the plasmid to segregating structures, such as the nuclear envelope and telomeres.
The morphology and brevity of mitotic division in budding yeast impose physical constraints on the diffusion of material into the daughter, obviating the need for a retention mechanism to generate rejuvenated offspring.