ABERRANT MITOSIS IN FISSION YEAST MUTANTS DEFECTIVE IN FATTY-ACID SYNTHETASE AND ACETYL COA CARBOXYLASE

Two fission yeast temperature-sensitive mutants, Cut6 and Isn1, show a defect in nuclear division. The daughter nuclei differ dramatically i n size (the phenotype designated Isd, large and small daughter), Fluor escence in situ hybridization (FISH) revealed that sister chromatids w ere separated in the Isd cells, but appeared highly compact in one of the two daughter nuclei. EM showed asymmetric nuclear elongation follo wed by unequal separation of nonchromosomal nuclear structures in thes e mutant nuclei. The small nuclei lacked electron-dense nuclear materi als and contained highly compacted chromatin, The cut6(+) and Isd1(+) 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 Isd1(+) led to the Isd phenotype. Palmi tate in medium fully suppressed the phenotypes of Isd1. Cerulenin, an inhibitor for fatty acid synthesis, produced the Isd 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 nonchromosomal nuclear compone nts. We propose that fatty acid is directly or indirectly required for separating the mother nucleus into two equal daughters.