Nuclear envelope expansion is crucial for proper chromosomal segregation during a closed mitosis.

TitleNuclear envelope expansion is crucial for proper chromosomal segregation during a closed mitosis.
Publication TypeJournal Article
Year of Publication2016
AuthorsTakemoto A, Kawashima SA, Li J-J, Jeffery L, Yamatsugu K, Elemento O, Nurse P
JournalJ Cell Sci
Date Published2016 Mar 15
KeywordsCell Nucleus, Chromosome Segregation, Chromosomes, Fungal, Mitosis, Nuclear Envelope, Schizosaccharomyces, Schizosaccharomyces pombe Proteins

Here, we screened a 10,371 library of diverse molecules using a drug-sensitive fission yeast strain to identify compounds which cause defects in chromosome segregation during mitosis. We identified a phosphorium-ylide-based compound Cutin-1 which inhibits nuclear envelope expansion and nuclear elongation during the closed mitosis of fission yeast, and showed that its target is the β-subunit of fatty acid synthase. A point mutation in the dehydratase domain of Fas1 conferred in vivo and in vitro resistance to Cutin-1. Time-lapse photomicrography showed that the bulk of the chromosomes were only transiently separated during mitosis, and nucleoli separation was defective. Subsequently sister chromatids re-associated leading to chromosomal mis-segregation. These segregation defects were reduced when the nuclear volume was increased and were increased when the nuclear volume was reduced. We propose that there needs to be sufficient nuclear volume to allow the nuclear elongation necessary during a closed mitosis to take place for proper chromosome segregation, and that inhibition of fatty acid synthase compromises nuclear elongation and leads to defects in chromosomal segregation.

Alternate JournalJ. Cell. Sci.
PubMed ID26869222
PubMed Central IDPMC4813296
Grant List093917 / / Wellcome Trust / United Kingdom