scholarly journals Prolonged cyclin-dependent kinase inhibition results in septin perturbations during return to growth and mitosis

2018 ◽  
Vol 217 (7) ◽  
pp. 2429-2443 ◽  
Author(s):  
Gabriel M. Gihana ◽  
Tiffany R. Musser ◽  
Oscar Thompson ◽  
Soni Lacefield
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Normal Cell ◽  
Cyclin Dependent Kinase ◽  
Temporal Regulation ◽  
Developmental Program ◽  
M Phase ◽  
Multiple Buds ◽  
Diploid Cells ◽  
Normal Cell Cycle

We investigated how Saccharomyces cerevisiae coordinate polarization, budding, and anaphase during a unique developmental program called return to growth (RTG) in which cells in meiosis return to mitosis upon nutrient shift. Cells reentering mitosis from prophase I deviate from the normal cell cycle by budding in G2 instead of G1. We found that cells do not maintain the bipolar budding pattern, a characteristic of diploid cells. Furthermore, strict temporal regulation of M-phase cyclin-dependent kinase (CDK; M-CDK) is important for polarity establishment and morphogenesis. Cells with premature M-CDK activity caused by loss of checkpoint kinase Swe1 failed to polarize and underwent anaphase without budding. Mutants with increased Swe1-dependent M-CDK inhibition showed additional or more penetrant phenotypes in RTG than mitosis, including elongated buds, multiple buds, spindle mispositioning, and septin perturbation. Surprisingly, the enhanced and additional phenotypes were not exclusive to RTG but also occurred with prolonged Swe1-dependent CDK inhibition in mitosis. Our analysis reveals that prolonged activation of the Swe1-dependent checkpoint can be detrimental instead of beneficial.

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.

scholarly journals Three independent forms of regulation affect expression of HO, CLN1 and CLN2 during the cell cycle of Saccharomyces cerevisiae.

Genetics ◽  
1994 ◽  
Vol 138 (4) ◽  
pp. 1015-1024 ◽  
Author(s):  
L Breeden ◽  
G Mikesell
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Normal Cell ◽  
Cell Cycle Regulation ◽  
Cell Cycle Control ◽  
G1 Cyclins ◽  
Affect Expression ◽  
Cdc28 Kinase ◽  
Cycle Regulation ◽  
Normal Cell Cycle

Abstract The G1 cyclins (CLNs) bind to and activate the CDC28 kinase during the G1 to S transition in Saccharomyces cerevisiae. Two G1 cyclins are regulated at the RNA level so that their RNAs peak at the G1/S boundary. In this report we show that the cell cycle regulation of CLN1 and CLN2 is partially determined by the restricted expression of SW14, a known trans-activator of SCB elements. When SWI4 is constitutively expressed or deleted, cell cycle regulation of CLN1/2 is reduced but not eliminated. In the absence of SwI6, another known regulator of both SCB and MCB elements, cell cycle regulation of the CLNs is also reduced, and the Start-dependence of HO transcription is eliminated. This indicates that SwI6 also plays an important role in the normal cell cycle regulation of all three promoters. When both SwI6 activity and the transcriptional regulation of SW14 are eliminated, cell cycle regulation is further reduced, indicating that these are two independent pathways of regulation. However, a twofold fluctuation in transcript levels still persists under these conditions. This reveals a third source of cell cycle control, which could affect SwI4 activity post-transcriptionally, or reflect the existence of another unidentified regulator of these promoters.

scholarly journals Disturbance of normal cell cycle progression enhances the establishment of transcriptional silencing in Saccharomyces cerevisiae.

1995 ◽  
Vol 15 (7) ◽  
pp. 3608-3617 ◽  
Author(s):  
H Laman ◽  
D Balderes ◽  
D Shore
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Normal Cell ◽  
Cell Cycle Progression ◽  
Position Effect ◽  
General Effect ◽  
Cell Cycle Regulators ◽  
Cycle Progression ◽  
Cyclin Genes ◽  
Normal Cell Cycle

Previous studies have indicated that mutation of RAP1 (rap1s) or of the HMR-E silencer ARS consensus element leads to metastable repression of HMR. A number of extragenic suppressor mutations (sds, suppressors of defective silencing) that increase the fraction of repressed cells in rap1s hmr delta A strains have been identified. Here we report the cloning of three SDS genes. SDS11 is identical to SWI6, a transcriptional regulator of genes required for DNA replication and of cyclin genes. SDS12 is identical to RNR1, which encodes a subunit of ribonucleotide reductase. SDS15 is identical to CIN8, whose product is required for spindle formation. We propose that mutations in these genes improve the establishment of silencing by interfering with normal cell cycle progression. In support of this idea, we show that exposure to hydroxyurea, which increases the length of S phase, also restores silencing in rap1s hmr delta A strains. Mutations in different cyclin genes (CLN3, CLB5, and CLB2) and two cell cycle transcriptional regulators (SWI4 and MBP1) also suppress the silencing defect at HMR. The effect of these cell cycle regulators is not specific to the rap1s or hmr delta A mutation, since swi6, swi4, and clb5 mutations also suppress mutations in SIR1, another gene implicated in the establishment of silencing. Several mutations also improve the efficiency of telomeric silencing in wild-type strains, further demonstrating that disturbance of the cell cycle has a general effect on position effect repression in Saccharomyces cerevisiae. We suggest several possible models to explain this phenomenon.

scholarly journals Adenovirus E4orf4 protein induces PP2A-dependent growth arrest in Saccharomyces cerevisiae and interacts with the anaphase-promoting complex/cyclosome

2001 ◽  
Vol 154 (2) ◽  
pp. 331-344 ◽  
Author(s):  
Daniel Kornitzer ◽  
Rakefet Sharf ◽  
Tamar Kleinberger
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Mammalian Cells ◽  
Growth Arrest ◽  
Anaphase Promoting Complex ◽  
Reading Frame ◽  
Cycle Growth ◽  
M Phase ◽  
Dependent Growth ◽  
Synthetically Lethal

Adenovirus early region 4 open reading frame 4 (E4orf4) protein has been reported to induce p53-independent, protein phosphatase 2A (PP2A)–dependent apoptosis in transformed mammalian cells. In this report, we show that E4orf4 induces an irreversible growth arrest in Saccharomyces cerevisiae at the G2/M phase of the cell cycle. Growth inhibition requires the presence of yeast PP2A-Cdc55, and is accompanied by accumulation of reactive oxygen species. E4orf4 expression is synthetically lethal with mutants defective in mitosis, including Cdc28/Cdk1 and anaphase-promoting complex/cyclosome (APC/C) mutants. Although APC/C activity is inhibited in the presence of E4orf4, Cdc28/Cdk1 is activated and partially counteracts the E4orf4-induced cell cycle arrest. The E4orf4–PP2A complex physically interacts with the APC/C, suggesting that E4orf4 functions by directly targeting PP2A to the APC/C, thereby leading to its inactivation. Finally, we show that E4orf4 can induce G2/M arrest in mammalian cells before apoptosis, indicating that E4orf4-induced events in yeast and mammalian cells are highly conserved.

scholarly journals Ribosomal Protein S6 Gene Haploinsufficiency Is Associated with Activation of a p53-Dependent Checkpoint during Gastrulation

2006 ◽  
Vol 26 (23) ◽  
pp. 8880-8891 ◽  
Author(s):  
Linda Panić ◽  
Sanda Tamarut ◽  
Melanie Sticker-Jantscheff ◽  
Martina Barkić ◽  
Davor Solter ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Embryonic Development ◽  
Ribosomal Protein ◽  
Ribosome Biogenesis ◽  
Fetal Liver ◽  
Genetic Inactivation ◽  
Developmental Program ◽  
Ribosomal Protein S6 ◽  
M Phase ◽  
Insight Into

ABSTRACT Nascent ribosome biogenesis is required during cell growth. To gain insight into the importance of this process during mouse oogenesis and embryonic development, we deleted one allele of the ribosomal protein S6 gene in growing oocytes and generated S6-heterozygous embryos. Oogenesis and embryonic development until embryonic day 5.5 (E5.5) were normal. However, inhibition of entry into M phase of the cell cycle and apoptosis became evident post-E5.5 and led to perigastrulation lethality. Genetic inactivation of p53 bypassed this checkpoint and prolonged development until E12.5, when the embryos died, showing decreased expression of D-type cyclins, diminished fetal liver erythropoiesis, and placental defects. Thus, a p53-dependent checkpoint is activated during gastrulation in response to ribosome insufficiency to prevent improper execution of the developmental program.

scholarly journals Oncogenes - the basics

2018 ◽  
Vol 3 (4) ◽  
pp. 35-37
Author(s):  
Arnab Ghosh ◽  
Diasma Ghartimagar ◽  
Sushma Thapa
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Repair ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Normal Cell ◽  
Tumor Formation ◽  
Precursor Cell ◽  
Single Precursor ◽  
Normal Cell Cycle

Normal cell cycle and cell proliferation are regulated by several genes which can be broadly classified into 4 groups viz, proto-oncogenes, tumor suppressor genes, genes regulating apoptosis and genes involved in DNA repair. These genes may be defective due to different factors. The defective genes may lead to production of abnormal proteins which may lead to disruption of the normal cell cycle and proliferation. A single precursor cell with defective gene proliferates surpassing the normal physiologic regulatory process and leads to tumor formation, so, traditionally,it is said that “tumors are clonal”.

scholarly journals Posttranslational Phosphorylation and Ubiquitination of the Saccharomyces cerevisiae Poly(A) Polymerase at the S/G2 Stage of the Cell Cycle

2000 ◽  
Vol 20 (8) ◽  
pp. 2794-2802 ◽  
Author(s):  
Neptune Mizrahi ◽  
Claire Moore
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Cell Sorting ◽  
S Phase ◽  
Phase Arrest ◽  
Phosphatase Treatment ◽  
M Phase ◽  
64 Kda Protein ◽  
Mitotic Phosphorylation ◽  
Cycle Regulation

ABSTRACT The poly(A) polymerase of the budding yeast Saccharomyces cerevisiae (Pap1) is a 64-kDa protein essential for the maturation of mRNA. We have found that a modified Pap1 of 90 kDa transiently appears in cells after release from α-factor-induced G1 arrest or from a hydroxyurea-induced S-phase arrest. While a small amount of modification occurs in hydroxyurea-arrested cells, fluorescence-activated cell sorting analysis and microscopic examination of bud formation indicate that the majority of modified enzyme is found at late S/G2 and disappears by the time cells have reached M phase. The reduction of the 90-kDa product upon phosphatase treatment indicates that the altered mobility is due to phosphorylation. A preparation containing primarily the phosphorylated Pap1 has no poly(A) addition activity, but this activity is restored by phosphatase treatment. A portion of Pap1 is also polyubiquitinated concurrent with phosphorylation. However, the bulk of the 64-kDa Pap1 is a stable protein with a half-life of 14 h. The timing, nature, and extent of Pap1 modification in comparison to the mitotic phosphorylation of mammalian poly(A) polymerase suggest an intriguing difference in the cell cycle regulation of this enzyme in yeast and mammalian systems.

Nucleoside diphosphokinase, an enzyme with step changes in activity during the cell cycle of the fission yeast Schizosaccharomyces pombe. I. Persistence of steps after a block to the DNA-division cycle

1986 ◽  
Vol 86 (1) ◽  
pp. 207-215
Author(s):  
J. Creanor ◽  
J.M. Mitchison
Keyword(s):  
Cell Cycle ◽  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Normal Cell ◽  
Normal Cell Cycle

In confirmation of earlier results, nucleoside diphosphokinase is shown to be a ‘step’ enzyme in Schizosaccharomyces pombe with a sharp doubling in activity at the beginning of the cell cycle. These doubling steps occur at the same time in the cycle in the smaller cells of the mutant wee1.6. An important result is that the activity steps persist with normal cell cycle timing after a block to the DNA-division cycle imposed by the cycle mutants cdc2.33 and cdc2.33wee1.6. This is clear proof that oscillatory controls of some cell cycle events can persist after the main periodic events of the DNA-division cycle have been abolished.

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