scholarly journals The budding yeast Start repressor Whi7 differs in regulation from Whi5, emerging as a major cell cycle brake in response to stress

2020 ◽  
Vol 133 (24) ◽  
pp. jcs251413
Author(s):  
Ester Méndez ◽  
Mercè Gomar-Alba ◽  
M. Carmen Bañó ◽  
Manuel Mendoza ◽  
Inma Quilis ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Budding Yeast ◽  
Wall Stress ◽  
Eukaryotic Cell ◽  
Transcriptional Repressors ◽  
Decision Point ◽  
Cell Wall Stress ◽  
Comprehensive Comparison ◽  
Response To Stress ◽  
First Time

ABSTRACTStart is the main decision point in the eukaryotic cell cycle at which cells commit to a new round of cell division. It involves the irreversible activation of a transcriptional programme through the inactivation of Start transcriptional repressors: the retinoblastoma family in mammals, or Whi5 and its recently identified paralogue Whi7 (also known as Srl3) in budding yeast. Here, we provide a comprehensive comparison of Whi5 and Whi7 that reveals significant qualitative differences. Indeed, the expression, subcellular localization and functionality of Whi7 and Whi5 are differentially regulated. Importantly, Whi7 shows specific properties in its association with promoters not shared by Whi5, and for the first time, we demonstrate that Whi7, and not Whi5, can be the main contributor to Start inhibition such as it occurs in the response to cell wall stress. Our results help to improve understanding of the interplay between multiple differentially regulated Start repressors in order to face specific cellular conditions.

scholarly journals Quantitative Characterization of a Mitotic Cyclin Threshold Regulating Exit from Mitosis

2005 ◽  
Vol 16 (5) ◽  
pp. 2129-2138 ◽  
Author(s):  
Frederick R. Cross ◽  
Lea Schroeder ◽  
Martin Kruse ◽  
Katherine C. Chen
Keyword(s):  
Cell Cycle ◽  
Budding Yeast ◽  
Cell Cycle Control ◽  
Predictive Ability ◽  
Eukaryotic Cell ◽  
Model Predictions ◽  
Mitotic Cyclin ◽  
Constitutive Overexpression

Regulation of cyclin abundance is central to eukaryotic cell cycle control. Strong overexpression of mitotic cyclins is known to lock the system in mitosis, but the quantitative behavior of the control system as this threshold is approached has only been characterized in the in vitro Xenopus extract system. Here, we quantitate the threshold for mitotic block in budding yeast caused by constitutive overexpression of the mitotic cyclin Clb2. Near this threshold, the system displays marked loss of robustness, in that loss or even heterozygosity for some regulators becomes deleterious or lethal, even though complete loss of these regulators is tolerated at normal cyclin expression levels. Recently, we presented a quantitative kinetic model of the budding yeast cell cycle. Here, we use this model to generate biochemical predictions for Clb2 levels, asynchronous as well as through the cell cycle, as the Clb2 overexpression threshold is approached. The model predictions compare well with biochemical data, even though no data of this type were available during model generation. The loss of robustness of the Clb2 overexpressing system is also predicted by the model. These results provide strong confirmation of the model's predictive ability.

scholarly journals Using Budding Yeast to Identify Molecules That Block Cancer Cell ‘Mitotic Slippage’ Only in the Presence of Mitotic Poisons

2021 ◽  
Vol 22 (15) ◽  
pp. 7985
Author(s):  
Scott C. Schuyler ◽  
Hsin-Yu Chen
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Drug Targets ◽  
Budding Yeast ◽  
Eukaryotic Cell ◽  
Mitotic Checkpoint ◽  
Chemotherapeutic Agents ◽  
Cell Cycle Checkpoints ◽  
Yeast Saccharomyces Cerevisiae ◽  
Mitotic Slippage

Research on the budding yeast Saccharomyces cerevisiae has yielded fundamental discoveries on highly conserved biological pathways and yeast remains the best-studied eukaryotic cell in the world. Studies on the mitotic cell cycle and the discovery of cell cycle checkpoints in budding yeast has led to a detailed, although incomplete, understanding of eukaryotic cell cycle progression. In multicellular eukaryotic organisms, uncontrolled aberrant cell division is the defining feature of cancer. Some of the most successful classes of anti-cancer chemotherapeutic agents are mitotic poisons. Mitotic poisons are thought to function by inducing a mitotic spindle checkpoint-dependent cell cycle arrest, via the assembly of the highly conserved mitotic checkpoint complex (MCC), leading to apoptosis. Even in the presence of mitotic poisons, some cancer cells continue cell division via ‘mitotic slippage’, which may correlate with a cancer becoming refractory to mitotic poison chemotherapeutic treatments. In this review, knowledge about budding yeast cell cycle control is explored to suggest novel potential drug targets, namely, specific regions in the highly conserved anaphase-promoting complex/cyclosome (APC/C) subunits Apc1 and/or Apc5, and in a specific N-terminal region in the APC/C co-factor cell division cycle 20 (Cdc20), which may yield molecules which block ‘mitotic slippage’ only in the presence of mitotic poisons.

G1 cyclins regulate proliferation of the budding yeast Saccharomyces cerevisiae

1992 ◽  
Vol 70 (10-11) ◽  
pp. 946-953
Author(s):  
Adele Rowley ◽  
Gerald C. Johnston ◽  
Richard A. Singer
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Protein Kinase ◽  
Budding Yeast ◽  
Cell Types ◽  
Eukaryotic Cell ◽  
Yeast Saccharomyces Cerevisiae ◽  
Functional Conservation ◽  
Cycle Regulation

The eukaryotic cell cycle is regulated at two points, the G1-S and G2-M boundaries. The molecular basis for these regulatory activities has recently been elucidated, in large part by the use of molecular and genetic analyses using unicellular yeast. The molecular characterization of cell-cycle regulation has revealed striking functional conservation among evolutionarily diverse cell types. For many eukaryotic cells, regulation of cell proliferation occurs primarily in the G1 interval. The G2 regulatory step, termed start, requires the activation of a highly conserved p34 protein kinase by association with a functionally redundant family of proteins, the G1 cyclins. Here we review studies using the genetically tractable budding yeast Saccharomyces cerevisiae, which have provided insight into the role of G1 cyclins in the regulation of start.Key words: cell cycle, cyclin proteins, cdc2 protein kinase, start.

scholarly journals Quantitative model of eukaryotic Cdk control through the Forkhead CONTROLLER

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Matteo Barberis
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Cell Division ◽  
Design Principle ◽  
Budding Yeast ◽  
Eukaryotic Cell ◽  
Quantitative Model ◽  
Sequential Order ◽  
Forkhead Transcription Factors

AbstractIn budding yeast, synchronization of waves of mitotic cyclins that activate the Cdk1 kinase occur through Forkhead transcription factors. These molecules act as controllers of their sequential order and may account for the separation in time of incompatible processes. Here, a Forkhead-mediated design principle underlying the quantitative model of Cdk control is proposed for budding yeast. This design rationalizes timing of cell division, through progressive and coordinated cyclin/Cdk-mediated phosphorylation of Forkhead, and autonomous cyclin/Cdk oscillations. A “clock unit” incorporating this design that regulates timing of cell division is proposed for both yeast and mammals, and has a DRIVER operating the incompatible processes that is instructed by multiple CLOCKS. TIMERS determine whether the clocks are active, whereas CONTROLLERS determine how quickly the clocks shall function depending on external MODULATORS. This “clock unit” may coordinate temporal waves of cyclin/Cdk concentration/activity in the eukaryotic cell cycle making the driver operate the incompatible processes, at separate times.

scholarly journals Cohesin dysfunction results in cell wall defects in budding yeast

Genetics ◽  
2020 ◽  
Vol 217 (1) ◽  
pp. 1-16
Author(s):  
Deepash Kothiwal ◽  
Swagathnath Gopinath ◽  
Shikha Laloraya
Keyword(s):  
Cell Wall ◽  
Genetic Interaction ◽  
Interaction Analysis ◽  
Budding Yeast ◽  
Mapk Pathway ◽  
Regulation Of Gene Expression ◽  
Wall Stress ◽  
Dependent Manner ◽  
Cell Wall Stress ◽  
Cell Wall Organization

Abstract Cohesin is a conserved chromatin-binding multisubunit protein complex involved in diverse chromosomal transactions such as sister-chromatid cohesion, chromosome condensation, regulation of gene expression, DNA replication, and repair. While working with a budding yeast temperature-sensitive mutant, mcd1-1, defective in a cohesin subunit, we observed that it was resistant to zymolyase, indicating an altered cell wall organization. The budding yeast cell wall is a strong but elastic structure essential for maintenance of cell shape and protection from extreme environmental challenges. Here, we show that the cohesin complex plays an important role in cell wall maintenance. Cohesin mutants showed high chitin content in the cell wall and sensitivity to multiple cell wall stress-inducing agents. Interestingly, temperature-dependent lethality of cohesin mutants was osmoremedial, in a HOG1-MAPK pathway-dependent manner, suggesting that the temperature sensitivity of these mutants may arise partially from cell wall defects. Moreover, Mpk1 hyper-phosphorylation indicated activation of the cell wall integrity (CWI) signaling pathway in cohesin mutants. Genetic interaction analysis revealed that the CWI pathway is essential for survival of mcd1-1 upon additional cell wall stress. The cell wall defect was independent of the cohesion function and accompanied by misregulation of expression of several genes having cell wall-related functions. Our findings reveal a requirement of cohesin in maintenance of CWI that is independent of the CWI pathway, and that may arise from cohesin’s role in regulating the expression of multiple genes encoding proteins involved in cell wall organization and biosynthesis.

scholarly journals Dual control by Cdk1 phosphorylation of the budding yeast APC/C ubiquitin ligase activator Cdh1

2016 ◽  
Vol 27 (14) ◽  
pp. 2198-2212 ◽  
Author(s):  
Sebastian Höckner ◽  
Lea Neumann-Arnold ◽  
Wolfgang Seufert
Keyword(s):  
Cell Cycle ◽  
Ubiquitin Ligase ◽  
Budding Yeast ◽  
Cell Cycle Control ◽  
Eukaryotic Cell ◽  
Negative Control ◽  
Nuclear Localization Sequence ◽  
Phosphorylation Sites ◽  
Localization Sequence ◽  
Cdk Phosphorylation

The antagonism between cyclin-dependent kinases (Cdks) and the ubiquitin ligase APC/C-Cdh1 is central to eukaryotic cell cycle control. APC/C-Cdh1 targets cyclin B and other regulatory proteins for degradation, whereas Cdks disable APC/C-Cdh1 through phosphorylation of the Cdh1 activator protein at multiple sites. Budding yeast Cdh1 carries nine Cdk phosphorylation sites in its N-terminal regulatory domain, most or all of which contribute to inhibition. However, the precise role of individual sites has remained unclear. Here, we report that the Cdk phosphorylation sites of yeast Cdh1 are organized into autonomous subgroups and act through separate mechanisms. Cdk sites 1–3 had no direct effect on the APC/C binding of Cdh1 but inactivated a bipartite nuclear localization sequence (NLS) and thereby controlled the partitioning of Cdh1 between cytoplasm and nucleus. In contrast, Cdk sites 4–9 did not influence the cell cycle–regulated localization of Cdh1 but prevented its binding to the APC/C. Cdk sites 4–9 reside near two recently identified APC/C interaction motifs in a pattern conserved with the human Cdh1 orthologue. Thus a Cdk-inhibited NLS goes along with Cdk-inhibited APC/C binding sites in yeast Cdh1 to relay the negative control by Cdk1 phosphorylation of the ubiquitin ligase APC/C-Cdh1.

scholarly journals Abundances of transcripts, proteins, and metabolites in the cell cycle of budding yeast reveals coordinate control of lipid metabolism

2019 ◽  
Author(s):  
Heidi M. Blank ◽  
Ophelia Papoulas ◽  
Nairita Maitra ◽  
Riddhiman Garge ◽  
Brian K. Kennedy ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Lipid Metabolism ◽  
Cell Division ◽  
Ribosome Biogenesis ◽  
Budding Yeast ◽  
Eukaryotic Cell ◽  
Yeast Cells ◽  
Protein Levels ◽  
Coordinate Control ◽  
Cycle Dependent

ABSTRACTEstablishing the pattern of abundance of molecules of interest during cell division has been a long-standing goal of cell cycle studies. In several systems, including the budding yeast Saccharomyces cerevisiae, cell cycle-dependent changes in the transcriptome are well studied. In contrast, few studies queried the proteome during cell division, and they are often plagued by low agreement with each other and with previous transcriptomic datasets. There is also little information about dynamic changes in the levels of metabolites and lipids in the cell cycle. Here, for the first time in any system, we present experiment-matched datasets of the levels of RNAs, proteins, metabolites, and lipids from un-arrested, growing, and synchronously dividing yeast cells. Overall, transcript and protein levels were correlated, but specific processes that appeared to change at the RNA level (e.g., ribosome biogenesis), did not do so at the protein level, and vice versa. We also found no significant changes in codon usage or the ribosome content during the cell cycle. We describe an unexpected mitotic peak in the abundance of ergosterol and thiamine biosynthesis enzymes. Although the levels of several metabolites changed in the cell cycle, by far the most significant changes were in the lipid repertoire, with phospholipids and triglycerides peaking strongly late in the cell cycle. Our findings provide an integrated view of the abundance of biomolecules in the eukaryotic cell cycle and point to a coordinate mitotic control of lipid metabolism.

scholarly journals Cyclin/Forkhead-mediated coordination of cyclin waves: an autonomous oscillator rationalizing the quantitative model of Cdk control for budding yeast

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Matteo Barberis
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Current Knowledge ◽  
Budding Yeast ◽  
Cell Cycle Control ◽  
Eukaryotic Cell ◽  
Quantitative Model ◽  
Forkhead Transcription Factors ◽  
Dynamic Coordination ◽  
Cell Cycle Dynamics

AbstractNetworks of interacting molecules organize topology, amount, and timing of biological functions. Systems biology concepts required to pin down ‘network motifs’ or ‘design principles’ for time-dependent processes have been developed for the cell division cycle, through integration of predictive computer modeling with quantitative experimentation. A dynamic coordination of sequential waves of cyclin-dependent kinases (cyclin/Cdk) with the transcription factors network offers insights to investigate how incompatible processes are kept separate in time during the eukaryotic cell cycle. Here this coordination is discussed for the Forkhead transcription factors in light of missing gaps in the current knowledge of cell cycle control in budding yeast. An emergent design principle is proposed where cyclin waves are synchronized by a cyclin/Cdk-mediated feed-forward regulation through the Forkhead as a transcriptional timer. This design is rationalized by the bidirectional interaction between mitotic cyclins and the Forkhead transcriptional timer, resulting in an autonomous oscillator that may be instrumental for a well-timed progression throughout the cell cycle. The regulation centered around the cyclin/Cdk–Forkhead axis can be pivotal to timely coordinate cell cycle dynamics, thereby to actuate the quantitative model of Cdk control.

Sign in / Sign up

Export Citation Format

Share Document