Translational control of lipogenesis links protein synthesis and phosphoinositide signaling with nuclear division in Saccharomyces cerevisiae

Genetics ◽  
2021 ◽  
Author(s):  
Nairita Maitra ◽  
Staci Hammer ◽  
Clara Kjerfve ◽  
Vytas A Bankaitis ◽  
Michael Polymenis
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Signaling Pathways ◽  
Translational Control ◽  
Fatty Acid Synthase ◽  
Nuclear Division ◽  
Lipid Synthesis ◽  
Yeast Cells ◽  
Phosphoinositide Signaling ◽  
Eukaryotic Organism

Abstract Continuously dividing cells coordinate their growth and division. How fast cells grow in mass determines how fast they will multiply. Yet, there are few, if any, examples of a metabolic pathway that actively drives a cell cycle event instead of just being required for it. Here, we show that translational upregulation of lipogenic enzymes in Saccharomyces cerevisiae increased the abundance of lipids and promoted nuclear elongation and division. De-repressing translation of acetyl CoA carboxylase and fatty acid synthase also suppressed cell cycle-related phenotypes, including delayed nuclear division, associated with Sec14p phosphatidylinositol transfer protein deficiencies, and the irregular nuclear morphologies of mutants defective in phosphatidylinositol 4-OH kinase activities. Our results show that increased lipogenesis drives a critical cell cycle landmark and report a phosphoinositide signaling axis in control of nuclear division. The broad conservation of these lipid metabolic and signaling pathways raises the possibility these activities similarly govern nuclear division in other eukaryotes. In this report, the authors show that increasing lipid synthesis promotes the division of the nucleus in yeast cells, a model eukaryotic organism. They also implicate phosphoinositide signaling in the control of nuclear division. Because lipid metabolic and signaling pathways are highly conserved, it is possible that these activities also control nuclear division in other organisms. AUTHOR SUMMARY In this report, the authors show that increasing lipid synthesis promotes the division of the nucleus in yeast cells, a model eukaryotic organism. They also implicate phosphoinositide signaling in the control of nuclear division. Because lipid metabolic and signaling pathways are highly conserved, it is possible that these activities also control nuclear division in other organisms.

scholarly journals Translational control of lipogenesis links protein synthesis and phosphoinositide signaling with nuclear division

2021 ◽  
Author(s):  
Nairita Maitra ◽  
Staci Hammer ◽  
Clara Kjerfve ◽  
Vytas A. Bankaitis ◽  
Michael Polymenis
Keyword(s):  
Cell Cycle ◽  
Translational Control ◽  
Fatty Acid Synthase ◽  
Nuclear Division ◽  
Phosphoinositide Signaling ◽  
Signaling Axis ◽  
Dividing Cells ◽  
A Cell ◽  
Phosphatidylinositol Transfer ◽  
Phosphatidylinositol 4

ABSTRACTContinuously dividing cells coordinate their growth and division. How fast cells grow in mass determines how fast they will multiply. Yet, there are few, if any, examples of a metabolic pathway that actively drives a cell cycle event instead of just being required for it. Here, we show that translational upregulation of lipogenic enzymes in yeast increased the abundance of lipids and accelerated nuclear elongation and division. De-repressing translation of acetyl CoA carboxylase and fatty acid synthase also suppressed cell cycle-related phenotypes, including delayed nuclear division, associated with Sec14p phosphatidylinositol transfer protein deficiencies, and the irregular nuclear morphologies of mutants defective in phosphatidylinositol 4-OH kinase activities. Our results show that increased lipogenesis drives a critical cell cycle landmark and report a phosphoinositide signaling axis in control of nuclear division. The broad conservation of these lipid metabolic and signaling pathways raises the possibility these activities similarly govern nuclear division in mammals.

Inhibition by sulfanilamide of sporulation in Saccharomyces cerevisiae

1977 ◽  
Vol 23 (6) ◽  
pp. 659-671 ◽  
Author(s):  
William J. Colonna ◽  
James M. Gentile ◽  
P. T. Magee
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Vegetative Growth ◽  
Nuclear Division ◽  
Glycogen Synthesis ◽  
Yeast Cells ◽  
Progressive Reduction ◽  
Yeast Strains ◽  
Sporulation Process ◽  
Drug Arrests

The antimetabolite sulfanilamide inhibits sporulation in Saccharomyces cerevisiae strain API. Cells exposed to sulfanilamide at various times during the sporulation process become progressively insensitive to the drug, although accumulation of sulfanilamide by the cells increases with time. Vegetative growth of API is practically unaffected by sulfanilamide; pregrowth of the cells in the presence of the drug does not prevent sporulation. Thus, inhibition is confined to the meiotic phase of the cell cycle. Sensitivity to sulfanilamide is independent of pH. Increasing the time cells are exposed to sulfanilamide results in a progressive reduction of ascus formation; however, the inhibition is reversible since sporulation can occur in cells exposed to the drug for > 24 h. The drug arrests the cells at a point before commitment to sporulation, since yeast cells exposed to sulfanilamide for 12 h do not complete the sporulation process when returned to vegetative medium, but resume mitotic growth instead. Meiotic nuclear division is largely prevented by sulfanilamide, and synthesis of RNA and protein is severely retarded. DNA synthesis is inhibited up to 50%; glycogen synthesis is ~90% inhibited. Other yeast strains showed varying sensitivity to sulfanilamide; homothallic strains were generally less affected.

scholarly journals Translational control of lipogenic enzymes in the cell cycle of synchronous, growing yeast cells

2017 ◽  
Vol 36 (4) ◽  
pp. 487-502 ◽  
Author(s):  
Heidi M Blank ◽  
Ricardo Perez ◽  
Chong He ◽  
Nairita Maitra ◽  
Richard Metz ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Translational Control ◽  
Yeast Cells ◽  
Lipogenic Enzymes

scholarly journals The spindle checkpoint protein Mad2 regulates APC/C activity during prometaphase and metaphase of meiosis I in Saccharomyces cerevisiae

2011 ◽  
Vol 22 (16) ◽  
pp. 2848-2861 ◽  
Author(s):  
Dai Tsuchiya ◽  
Claire Gonzalez ◽  
Soni Lacefield
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Chromosome Segregation ◽  
Meiotic Division ◽  
Spindle Checkpoint ◽  
Yeast Cells ◽  
Meiotic Cell ◽  
Checkpoint Protein ◽  
Sister Chromatids ◽  
Meiosis I

In many eukaryotes, disruption of the spindle checkpoint protein Mad2 results in an increase in meiosis I nondisjunction, suggesting that Mad2 has a conserved role in ensuring faithful chromosome segregation in meiosis. To characterize the meiotic function of Mad2, we analyzed individual budding yeast cells undergoing meiosis. We find that Mad2 sets the duration of meiosis I by regulating the activity of APCCdc20. In the absence of Mad2, most cells undergo both meiotic divisions, but securin, a substrate of the APC/C, is degraded prematurely, and prometaphase I/metaphase I is accelerated. Some mad2Δ cells have a misregulation of meiotic cell cycle events and undergo a single aberrant division in which sister chromatids separate. In these cells, both APCCdc20 and APCAma1 are prematurely active, and meiosis I and meiosis II events occur in a single meiotic division. We show that Mad2 indirectly regulates APCAma1 activity by decreasing APCCdc20 activity. We propose that Mad2 is an important meiotic cell cycle regulator that ensures the timely degradation of APC/C substrates and the proper orchestration of the meiotic divisions.

scholarly journals Requirement for ESP1 in the nuclear division of Saccharomyces cerevisiae.

1992 ◽  
Vol 3 (12) ◽  
pp. 1443-1454 ◽  
Author(s):  
J T McGrew ◽  
L Goetsch ◽  
B Byers ◽  
P Baum
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Normal Cell ◽  
Cell Cycle Progression ◽  
Nuclear Division ◽  
Flow Cytometric Analysis ◽  
Spindle Pole ◽  
Spindle Pole Bodies ◽  
Mutant Cells ◽  
Normal Cell Cycle

Mutations in the ESP1 gene of Saccharomyces cerevisiae disrupt normal cell-cycle control and cause many cells in a mutant population to accumulate extra spindle pole bodies. To determine the stage at which the esp1 gene product becomes essential for normal cell-cycle progression, synchronous cultures of ESP1 mutant cells were exposed to the nonpermissive temperature for various periods of time. The mutant cells retained viability until the onset of mitosis, when their viability dropped markedly. Examination of these cells by fluorescence and electron microscopy showed the first detectable defect to be a structural failure in the spindle. Additionally, flow cytometric analysis of DNA content demonstrated that massive chromosome missegregation accompanied this failure of spindle function. Cytokinesis occurred despite the aberrant nuclear division, which often resulted in segregation of both spindle poles to the same cell. At later times, the missegregated spindle pole bodies entered a new cycle of duplication, thereby leading to the accumulation of extra spindle pole bodies within a single nucleus. The DNA sequence predicts a protein product similar to those of two other genes that are also required for nuclear division: the cut1 gene of Schizosaccharomyces pombe and the bimB gene of Aspergillus nidulans.

The product of the Saccharomyces cerevisiae cell cycle gene DBF2 has homology with protein kinases and is periodically expressed in the cell cycle

1990 ◽  
Vol 10 (4) ◽  
pp. 1358-1366
Author(s):  
L H Johnston ◽  
S L Eberly ◽  
J W Chapman ◽  
H Araki ◽  
A Sugino
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Dna Synthesis ◽  
Protein Kinases ◽  
Nuclear Division ◽  
Cell Cycle Gene ◽  
Restrictive Temperature ◽  
Histone H2a ◽  
Reading Frame ◽  
Polymerase I

Several Saccharomyces cerevisiae dbf mutants defective in DNA synthesis have been described previously. In this paper, one of them, dbf2, is characterized in detail. The DBF2 gene has been cloned and mapped, and its nucleotide sequence has been determined. This process has identified an open reading frame capable of encoding a protein of molecular weight 64,883 (561 amino acids). The deduced amino acid sequence contains all 11 conserved domains found in various protein kinases. DBF2 was periodically expressed in the cell cycle at a time that clearly differed from the time of expression of either the histone H2A or DNA polymerase I gene. Its first function was completed very near to initiation of DNA synthesis. However, DNA synthesis in the mutant was only delayed at 37 degrees C, and the cells blocked in nuclear division. Consistent with this finding, the execution point occurred about 1 h after DNA synthesis, and the nuclear morphology of the mutant at the restrictive temperature was that of cells blocked in late nuclear division. DBF2 is therefore likely to encode a protein kinase that may function in initiation of DNA synthesis and also in late nuclear division.

Characterization of RAD9 of Saccharomyces cerevisiae and evidence that its function acts posttranslationally in cell cycle arrest after DNA damage

1990 ◽  
Vol 10 (12) ◽  
pp. 6554-6564
Author(s):  
T A Weinert ◽  
L H Hartwell
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Dna Sequence ◽  
Negative Regulator ◽  
Yeast Cells ◽  
Protein Synthesis Inhibitor ◽  
Cycle Arrest ◽  
Delta Cells

In eucaryotic cells, incompletely replicated or damaged chromosomes induce cell cycle arrest in G2 before mitosis, and in the yeast Saccharomyces cerevisiae the RAD9 gene is essential for the cell cycle arrest (T.A. Weinert and L. H. Hartwell, Science 241:317-322, 1988). In this report, we extend the analysis of RAD9-dependent cell cycle control. We found that both induction of RAD9-dependent arrest in G2 and recovery from arrest could occur in the presence of the protein synthesis inhibitor cycloheximide, showing that the mechanism of RAD9-dependent control involves a posttranslational mechanism(s). We have isolated and determined the DNA sequence of the RAD9 gene, confirming the DNA sequence reported previously (R. H. Schiestl, P. Reynolds, S. Prakash, and L. Prakash, Mol. Cell. Biol. 9:1882-1886, 1989). The predicted protein sequence for the Rad9 protein bears no similarity to sequences of known proteins. We also found that synthesis of the RAD9 transcript in the cell cycle was constitutive and not induced by X-irradiation. We constructed yeast cells containing a complete deletion of the RAD9 gene; the rad9 null mutants were viable, sensitive to X- and UV irradiation, and defective for cell cycle arrest after DNA damage. Although Rad+ and rad9 delta cells had similar growth rates and cell cycle kinetics in unirradiated cells, the spontaneous rate of chromosome loss (in unirradiated cells) was elevated 7- to 21-fold in rad9 delta cells. These studies show that in the presence of induced or endogenous DNA damage, RAD9 is a negative regulator that inhibits progression from G2 in order to preserve cell viability and to maintain the fidelity of chromosome transmission.

Polarization of cell growth in yeast. I. Establishment and maintenance of polarity states

2000 ◽  
Vol 113 (3) ◽  
pp. 365-375 ◽  
Author(s):  
D. Pruyne ◽  
A. Bretscher
Keyword(s):  
Cell Cycle ◽  
Yeast Cell ◽  
Signaling Pathways ◽  
Cell Polarity ◽  
Molecular Mechanisms ◽  
Fundamental Property ◽  
Yeast Cells ◽  
Cell Cortex ◽  
Yeast Saccharomyces Cerevisiae ◽  
Dependent Protein

The ability to polarize is a fundamental property of cells. The yeast Saccharomyces cerevisiae has proven to be a fertile ground for dissecting the molecular mechanisms that regulate cell polarity during growth. Here we discuss the signaling pathways that regulate polarity. In the second installment of this two-part commentary, which appears in the next issue of Journal of Cell Science, we discuss how the actin cytoskeleton responds to these signals and guides the polarity of essentially all events in the yeast cell cycle. During the cell cycle, yeast cells assume alternative states of polarized growth, which range from tightly focused apical growth to non-focused isotropic growth. RhoGTPases, and in particular Cdc42p, are essential to guiding this polarity. The distribution of Cdc42p at the cell cortex establishes cell polarity. Cyclin-dependent protein kinase, Ras, and heterotrimeric G proteins all modulate yeast cell polarity in part by altering the distribution of Cdc42p. In turn, Cdc42p generates feedback signals to these molecules in order to establish stable polarity states and coordinate cytoskeletal organization with the cell cycle. Given that many of these signaling pathways are present in both fungi and animals, they are probably ancient and conserved mechanisms for regulating polarity.

Overexpression of the STE4 gene leads to mating response in haploid Saccharomyces cerevisiae

1990 ◽  
Vol 10 (1) ◽  
pp. 217-222
Author(s):  
M Whiteway ◽  
L Hougan ◽  
D Y Thomas
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
G Protein ◽  
Gene Product ◽  
Beta Subunit ◽  
Yeast Cells ◽  
Pheromone Response ◽  
Mating Pheromone ◽  
Cycle Arrest

The STE4 gene of Saccharomyces cerevisiae encodes the beta subunit of the yeast pheromone receptor-coupled G protein. Overexpression of the STE4 protein led to cell cycle arrest of haploid cells. This arrest was like the arrest mediated by mating pheromones in that it led to similar morphological changes in the arrested cells. The arrest occurred in haploid cells of either mating type but not in MATa/MAT alpha diploids, and it was suppressed by defects in genes such as STE12 that are needed for pheromone response. Overexpression of the STE4 gene product also suppressed the sterility of cells defective in the mating pheromone receptors encoded by the STE2 and STE3 genes. Cell cycle arrest mediated by STE4 overexpression was prevented in cells that either were overexpressing the SCG1 gene product (the alpha subunit of the G protein) or lacked the STE18 gene product (the gamma subunit of the G protein). This finding suggests that in yeast cells, the beta subunit is the limiting component of the active beta gamma element and that a proper balance in the levels of the G-protein subunits is critical to a normal mating pheromone response.

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