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

• Published in: Journal of cell science Vol. 129; no. 6; pp. 1250 - 1259
• Main Authors: Takemoto, Ai, Kawashima, Shigehiro A, Li, Juan-Juan, Jeffery, Linda, Yamatsugu, Kenzo, Elemento, Olivier, Nurse, Paul
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 15-03-2016
• Subjects: Cell Nucleus - genetics; Cell Nucleus - metabolism; Chromosome Segregation; Chromosomes, Fungal - genetics; Chromosomes, Fungal - metabolism; Mitosis; Nuclear Envelope - genetics; Nuclear Envelope - metabolism; Schizosaccharomyces - cytology; Schizosaccharomyces - genetics; Schizosaccharomyces - metabolism; Schizosaccharomyces pombe Proteins - genetics; Schizosaccharomyces pombe Proteins - metabolism; Fatty acid synthase; Nuclear envelope expansion; Mitosis; Chromosome segregation
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.181560

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.