scholarly journals Multiple layers of phospho-regulation coordinate metabolism and the cell cycle in budding yeast

2019 ◽  
Author(s):  
Lichao Zhang ◽  
Sebastian Winkler ◽  
Fabian Schlottmann ◽  
Oliver Kohlbacher ◽  
Josh E. Elias ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Cycle Progression ◽  
Budding Yeast ◽  
Cell Metabolism ◽  
Acid Synthesis ◽  
Metabolic Enzymes ◽  
Cell Division Cycle ◽  
Amino Acid Synthesis ◽  
Metabolic Fluxes

AbstractThe coordination of metabolism and growth with cell division is crucial for proliferation. While it has long been known that cell metabolism regulates the cell division cycle, it is becoming increasingly clear that the cell division cycle also regulates metabolism. In budding yeast, we previously showed that over half of all measured metabolites change concentration through the cell cycle indicating that metabolic fluxes are extensively regulated during cell cycle progression. However, how this regulation is achieved still remains poorly understood. Since both the cell cycle and metabolism are regulated to a large extent by protein phosphorylation, we here decided to measure the phosphoproteome through the budding yeast cell cycle. Specifically, we chose a cell cycle synchronisation strategy that avoids stress and nutrient-related perturbations of metabolism, and we grew the yeast on ethanol minimal medium to force cells to utilize their full biosynthetic repertoire. Using a tandem-mass-tagging approach, we found over 200 sites on metabolic enzymes and transporters to be phospho-regulated. These sites were distributed among many pathways including carbohydrate catabolism, lipid metabolism and amino acid synthesis and therefore likely contribute to changing metabolic fluxes through the cell cycle. Among all one thousand sites whose phosphorylation increases through the cell cycle, the CDK consensus motif and an arginine-directed motif were highly enriched. This arginine-directed R-R-x-S motif is associated with protein-kinase A, which regulates metabolism and promotes growth. Finally, we also found over one thousand sites that are dephosphorylated through the G1/S transition. We speculate that the phosphatase Glc7/ PP1, known to regulate both the cell cycle and carbon metabolism, may play an important role because its regulatory subunits are phospho-regulated in our data. In summary, our results identify extensive cell cycle dependent phosphorylation and dephosphorylation of metabolic enzymes and suggest multiple mechanisms through which the cell division cycle regulates metabolic signalling pathways to temporally coordinate biosynthesis with distinct phases of the cell division cycle.

scholarly journals Analysis of Cell Cycle Progression in the Budding Yeast S. cerevisiae

2021 ◽  
pp. 265-276
Author(s):  
Deniz Pirincci Ercan ◽  
Frank Uhlmann
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Cycle Progression ◽  
Budding Yeast ◽  
Expression Profiles ◽  
Model Organisms ◽  
Cyclin Dependent Kinase ◽  
Cycle Progression ◽  
Daughter Cells ◽  
Substrate Phosphorylation

AbstractThe cell cycle is an ordered series of events by which cells grow and divide to give rise to two daughter cells. In eukaryotes, cyclin–cyclin-dependent kinase (cyclin–Cdk) complexes act as master regulators of the cell division cycle by phosphorylating numerous substrates. Their activity and expression profiles are regulated in time. The budding yeast S. cerevisiae was one of the pioneering model organisms to study the cell cycle. Its genetic amenability continues to make it a favorite model to decipher the principles of how changes in cyclin-Cdk activity translate into the intricate sequence of substrate phosphorylation events that govern the cell cycle. In this chapter, we introduce robust and straightforward methods to analyze cell cycle progression in S. cerevisiae. These techniques can be utilized to describe cell cycle events and to address the effects of perturbations on accurate and timely cell cycle progression.

scholarly journals Regulation of cell division cycle progression by bcl-2 expression: a potential mechanism for inhibition of programmed cell death.

1996 ◽  
Vol 183 (5) ◽  
pp. 2219-2226 ◽  
Author(s):  
S Mazel ◽  
D Burtrum ◽  
H T Petrie
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Division ◽  
Programmed Cell Death ◽  
Cell Cycle Progression ◽  
Control Point ◽  
Cell Division Cycle ◽  
Cell Cycle Distribution ◽  
Cycle Progression ◽  
Critical Control Point

Expression of the bcl-2 gene has been shown to effectively confer resistance to programmed cell death under a variety of circumstances. However, despite a wealth of literature describing this phenomenon, very little is known about the mechanism of resistance. In the experiments described here, we show that bcl-2 gene expression can result in an inhibition of cell division cycle progression. These findings are based upon the analysis of cell cycle distribution, cell cycle kinetics, and relative phosphorylation of the retinoblastoma tumor suppressor protein, using primary tissues in vivo, ex vivo, and in vitro, as well as continuous cell lines. The effects of bcl-2 expression on cell cycle progression appear to be focused at the G1 to S phase transition, which is a critical control point in the decision between continued cell cycle progression or the induction programmed cell death. In all systems tested, bcl-2 expression resulted in a substantial 30-60% increase in the length of G1 phase; such an increase is very substantial in the context of other regulators of cell cycle progression. Based upon our findings, and the related findings of others, we propose a mechanism by which bcl-2 expression might exert its well known inhibition of programmed cell death by regulating the kinetics of cell cycle progression at a critical control point.

Modelling the controls of the eukaryotic cell cycle

2003 ◽  
Vol 31 (6) ◽  
pp. 1526-1529 ◽  
Author(s):  
B. Novák ◽  
J.J. Tyson
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Mathematical Modelling ◽  
Dynamic Characteristics ◽  
Cell Cycle Progression ◽  
Eukaryotic Cell ◽  
Cell Division Cycle ◽  
Comprehensive Model ◽  
Cycle Progression

The eukaryotic cell-division cycle is regulated by three modules that control G1/S, G2/M and meta/anaphase transitions. By using mathematical modelling, we show the dynamic characteristics of these individual modules and we also assemble them together into a comprehensive model of the eukaryotic cell-division cycle. With this comprehensive model, we also discuss the mechanisms by which different checkpoint pathways stabilize different cell-cycle states and inhibit the transitions that drive cell-cycle progression.

scholarly journals An organelle inheritance pathway during polarized cell growth

2021 ◽  
Author(s):  
Kathryn W Li ◽  
Ross TA Pedersen ◽  
Michelle S Lu ◽  
David G Drubin
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Cycle Progression ◽  
Budding Yeast ◽  
Organelle Inheritance ◽  
Cycle Progression ◽  
Daughter Cells ◽  
Bud Emergence ◽  
Mother Cells ◽  
Cell Cycle Signaling

AbstractSome organelles cannot be synthesized anew, so they are segregated into daughter cells during cell division. In Saccharomyces cerevisiae, daughter cells bud from mother cells and are populated by organelles inherited from the mothers. To determine whether this organelle inheritance occurs in a stereotyped manner, we tracked organelles using fluorescence microscopy. We describe a program for organelle inheritance in budding yeast. The cortical endoplasmic reticulum (ER) and peroxisomes are inherited concomitant with bud emergence. Next, vacuoles are inherited in small buds, followed closely by mitochondria. Finally, the nucleus and perinuclear ER are inherited when buds have nearly reached their maximal size. Because organelle inheritance timing correlates with bud morphology, which is coupled to the cell cycle, we tested whether organelle inheritance order is controlled by the cell cycle. By arresting cell cycle progression but allowing continued bud growth, we determined that organelle inheritance still occurs without cell cycle progression past S-phase, and that the general inheritance order is maintained. Thus, organelle inheritance follows a preferred order during polarized cell division, but it is not controlled exclusively by cell cycle signaling.Summary statementOrganelles are interconnected by contact sites, but they must be inherited from mother cells into buds during budding yeast mitosis. We report that this process occurs in a preferred sequence.

scholarly journals Regulation of Cell Division in Bacteria by Monitoring Genome Integrity and DNA Replication Status

2019 ◽  
Vol 202 (2) ◽  
Author(s):  
Peter E. Burby ◽  
Lyle A. Simmons
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Division ◽  
Dna Replication ◽  
Cell Cycle Progression ◽  
Genome Instability ◽  
Sos Response ◽  
Bacterial Cells ◽  
Cycle Progression ◽  
Content Type

ABSTRACT All organisms regulate cell cycle progression by coordinating cell division with DNA replication status. In eukaryotes, DNA damage or problems with replication fork progression induce the DNA damage response (DDR), causing cyclin-dependent kinases to remain active, preventing further cell cycle progression until replication and repair are complete. In bacteria, cell division is coordinated with chromosome segregation, preventing cell division ring formation over the nucleoid in a process termed nucleoid occlusion. In addition to nucleoid occlusion, bacteria induce the SOS response after replication forks encounter DNA damage or impediments that slow or block their progression. During SOS induction, Escherichia coli expresses a cytoplasmic protein, SulA, that inhibits cell division by directly binding FtsZ. After the SOS response is turned off, SulA is degraded by Lon protease, allowing for cell division to resume. Recently, it has become clear that SulA is restricted to bacteria closely related to E. coli and that most bacteria enforce the DNA damage checkpoint by expressing a small integral membrane protein. Resumption of cell division is then mediated by membrane-bound proteases that cleave the cell division inhibitor. Further, many bacterial cells have mechanisms to inhibit cell division that are regulated independently from the canonical LexA-mediated SOS response. In this review, we discuss several pathways used by bacteria to prevent cell division from occurring when genome instability is detected or before the chromosome has been fully replicated and segregated.

scholarly journals Budding yeast relies on G1 cyclin specificity to couple cell cycle progression with morphogenetic development

2021 ◽  
Vol 7 (23) ◽  
pp. eabg0007
Author(s):  
Deniz Pirincci Ercan ◽  
Florine Chrétien ◽  
Probir Chakravarty ◽  
Helen R. Flynn ◽  
Ambrosius P. Snijders ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Budding Yeast ◽  
Quantitative Model ◽  
Cyclin Dependent Kinase ◽  
Cycle Progression ◽  
Model Cell ◽  
Mitotic Cyclin ◽  
Substrate Phosphorylation ◽  
The Cost

Two models have been put forward for cyclin-dependent kinase (Cdk) control of the cell cycle. In the qualitative model, cell cycle events are ordered by distinct substrate specificities of successive cyclin waves. Alternatively, in the quantitative model, the gradual rise of Cdk activity from G1 phase to mitosis leads to ordered substrate phosphorylation at sequential thresholds. Here, we study the relative contributions of qualitative and quantitative Cdk control in Saccharomyces cerevisiae. All S phase and mitotic cyclins can be replaced by a single mitotic cyclin, albeit at the cost of reduced fitness. A single cyclin can also replace all G1 cyclins to support ordered cell cycle progression, fulfilling key predictions of the quantitative model. However, single-cyclin cells fail to polarize or grow buds and thus cannot survive. Our results suggest that budding yeast has become dependent on G1 cyclin specificity to couple cell cycle progression to essential morphogenetic events.

scholarly journals The Cell Division Cycle of Euglena gracilis Indicates That the Level of Circadian Plasticity to the External Light Regime Changes in Prolonged-Stationary Cultures

Plants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1475
Author(s):  
Shota Kato ◽  
Hong Gil Nam
Keyword(s):  
Cell Division ◽  
Circadian Rhythms ◽  
Euglena Gracilis ◽  
Cell Cycle Progression ◽  
Light Signal ◽  
Cell Division Cycle ◽  
Regime Changes ◽  
Fitness Advantage ◽  
Subjective Night ◽  
Free Running

In unicellular photosynthetic organisms, circadian rhythm is tightly linked to gating of cell cycle progression, and is entrained by light signal. As several organisms obtain a fitness advantage when the external light/dark cycle matches their endogenous period, and aging alters circadian rhythms, senescence phenotypes of the microalga Euglena gracilis of different culture ages were characterized with respect to the cell division cycle. We report here the effects of prolonged-stationary-phase conditions on the cell division cycles of E. gracilis under non-24-h light/dark cycles (T-cycles). Under T-cycles, cells established from 1-month-old and 2-month-old cultures produced lower cell concentrations after cultivation in the fresh medium than cells from 1-week-old culture. This decrease was not due to higher concentrations of dead cells in the populations, suggesting that cells of different culture ages differ in their capacity for cell division. Cells from 1-week-old cultures had a shorter circadian period of their cell division cycle under shortened T-cycles than aged cells. When algae were transferred to free-running conditions after entrainment to shortened T-cycles, the young cells showed the peak growth rate at a time corresponding to the first subjective night, but the aged cells did not. This suggests that circadian rhythms are more plastic in younger E. gracilis cells.

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