Aberrant mitosis in fission yeast mutants defective in fatty acid synthetase and acetyl CoA carboxylase.
Two fission yeast temperature-sensitive mutants, cut6 and lsd1, show a defect in nuclear division. The daughter nuclei differ dramatically in size (the phenotype designated lsd, large and small daughter). Fluorescence in situ hybridization (FISH) revealed that sister chromatids were separated in the lsd cells, but appeared highly compact in one of the two daughter nuclei. EM showed asymmetric nuclear elongation followed by unequal separation of nonchromosomal nuclear structures in these mutant nuclei. The small nuclei lacked electron-dense nuclear materials and contained highly compacted chromatin. The cut6+ and lsd1+ genes are essential for viability and encode, respectively, acetyl CoA carboxylase and fatty acid synthetase, the key enzymes for fatty acid synthesis. Gene disruption of lsd1+ led to the lsd phenotype. Palmitate in medium fully suppressed the phenotypes of lsd1. Cerulenin, an inhibitor for fatty acid synthesis, produced the lsd phenotype in wild type. The drug caused cell inviability during mitosis but not during the G2-arrest induced by the cdc25 mutation. A reduced level of fatty acid thus led to impaired separation of non-chromosomal nuclear components. We propose that fatty acid is directly or indirectly required for separating the mother nucleus into two equal daughters.
Saitoh
S
S
Department of Biophysics, Faculty of Science, Kyoto University, Japan.
Takahashi
K
K
Nabeshima
K
K
Yamashita
Y
Y
Nakaseko
Y
Y
Hirata
A
A
Yanagida
M
M
D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D002455:Cell Division; D002467:Cell Nucleus / Q000648:ultrastructure; D002569:Cerulenin / Q000494:pharmacology; D015825:Chromosomes, Fungal; D003001:Cloning, Molecular; D004791:Enzyme Inhibitors / Q000494:pharmacology; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal / Q000235:genetics; D008938:Mitosis / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D010168:Palmitates / Q000494:pharmacology; D010641:Phenotype; D012568:Schizosaccharomyces / Q000166:cytology* / Q000201:enzymology / Q000235:genetics; D017422:Sequence Analysis, DNA; D013696:Temperature
D004791:Enzyme Inhibitors; D010168:Palmitates; D002569:Cerulenin; D064429:Fatty Acid Synthases; D000103:Acetyl-CoA Carboxylase