title: Nuclear geometry and rapid mitosis ensure asymmetric episome segregation in yeast.
abstract: BACKGROUND
  Asymmetric cell division drives the generation of differentiated cells and maintenance of stem cells. In budding yeast, autonomously replicating sequence (ARS) plasmids lacking centromere elements are asymmetrically segregated into the mother cell, where they are thought to contribute to cellular senescence. This phenomenon has been proposed to result from the active retention of plasmids through an interaction with nuclear pores.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
authors.forename: Lutz R
authors.initials: LR
authors.lastname: Gehlen
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nagai
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimada
authors.forename: Peter
authors.initials: P
authors.lastname: Meister
authors.forename: Angela
authors.initials: A
authors.lastname: Taddei
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gasser
mesh_terms: D002467:Cell Nucleus / Q000502:physiology*; D004261:DNA Replication; D008938:Mitosis / Q000502:physiology*; D008954:Models, Biological; D010957:Plasmids / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism*; D013997:Time Factors