Mutant enrichment of Schizosaccharomyces pombe by inositol-less death

Minskoff, Stacey A.; Gaynor, Paulette M.; Greenberg, Miriam L.

doi:10.1128/jb.174.12.4078-4085.1992

Cited by 14 publications

(12 citation statements)

References 17 publications

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“…These include an increase in the phosphatidylserine/phosphatidylinositol ratio in response to inositol starvation, and the ability of the organism to recycle inositol (Fernandez et al 1986). Furthermore, the inositol requirement of S. pombe depends on strain and cell concentration, and also varies with temperature and carbon source (Minsko et al 1992).…”

Section: Discussionmentioning

confidence: 99%

Alteration of the largest subunit of RNA polymerase II and its effect on chromosome stability in Schizosaccharomyces pombe

Sugaya¹,

Ajimura²,

Tsuji³

et al. 1998

Mol Gen Genet

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A mutation in the RNA polymerase II largest subunit (RpII LS) that is related to abnormal induction of sister chromatid exchange has previously been described the CHO-K1 cell mutant tsTM4. To elucidate the molecular basis of this effect we introduced the mutation into the homologous site in the Schizosaccharomyces pombe rpbl gene, which encodes RpII LS. Since the tsTM4 mutant exhibited a decrease in the rate of DNA synthesis in cells arrested in S phase at the nonpermissive temperature, we focussed on the study of growth, the cell cycle, and chromosome stability at various temperatures. First, we examined the effects of the mutation on haploid yeast cells. The mutant showed slower growth than the wild type, but cell growth was not arrested at the nonpermissive temperature. When growing cells were shifted to the nonpermissive temperature, an accumulation of cells in G1 and/or G0 was observed. Tetrad analysis suggested that these phenotypes were associated with the mutation. In diploid cells, chromosome instability was detected by loss of intragenic complementation between two alleles of the ade6 gene. An abnormal fraction of cells containing an intermediate DNA content was also observed by FACS analysis. The accumulation of this fraction may reflect the fact that a large number of cells are in S phase or have an abnormal DNA content as a result of chromosome instability. These observations demonstrate that the S. pombe rpb1 mutant exhibits a phenotype very similar to that of the CHO-K1 cell mutant tsTM4.

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Section: Discussionmentioning

confidence: 99%

Alteration of the largest subunit of RNA polymerase II and its effect on chromosome stability in Schizosaccharomyces pombe

Sugaya¹,

Ajimura²,

Tsuji³

et al. 1998

Mol Gen Genet

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“…Eukaryotic cells cannot survive without inositol, and die very rapidly when starved for this metabolite (28–30). Molecular studies in the yeast model system have elucidated complex regulatory mechanisms that sense and maintain inositol levels.…”

Section: The Importance Of Inositol As a Metabolic Sensormentioning

confidence: 99%

Myo‐inositol‐1‐phosphate (MIP) synthase: a possible new target for antibipolar drugs

et al. 2002

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Inositol metabolism is well characterized in yeast at a molecular level, and yeast is the only eukaryote in which genetic, molecular and functional genomic approaches to identify lithium. valproate and inositol targets may be combined readily. It has been shown that lithium inhibits yeast inositol monophosphatase (encoded by INM1 and INM2), and both valproate and lithium reduce intracellular inositol. Unlike lithium, valproate causes a decrease in intracellular inositol-1-phosphate as well. suggesting that myo-inositol-1-P (MIP) synthase is a site of valproate action in the yeast PI cycle. MIP synthase is the rate-limiting step in inositol biosynthesis and is highly regulated in response to inositol. Yeast genes that are affected by both lithium and valproate in the phosphoinositide pathways (INO1 increased over 10-fold, INO2 increased twofold and INM1 decreased about twofold) have been identified. It has also been reported previously that both lithium and inositol mildly up-regulate IMPA1 (encoding mammalian inositol monophosphatase) expression in human cells. These findings indicate that IMPA is regulated only mildly by lithium, and therefore may not be the major target in the inositol pathway. Given the substantial evidence for the role of inositol in the mechanism of action of lithium and valproate. the opposing and mild effects of lithium on the genes encoding inositol monophosphatase in yeast and human cells, but the powerful effect of lithium and valproate on INO1 in yeast, it is hypothesized that human hIANO1 is a factor in the psychopharmacology of mood stabilizers.

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“…The importance of inositol to eucaryotic cells is underscored by the phenomenon of inositol-less death, which ensues when inositol auxotrophs are starved for inositol (29,61,71,85,204,211). Inositol-less death occurs in S. pombe also (153,154). However, the degree of loss of viability is strain and cell concentration dependent and varies with temperature and carbon source (154).…”

Section: Schizosaccharomyces Pombementioning

confidence: 99%