scholarly journals Rate of cell cycle initiation of yeast cells when cell size is not a rate-determining factor

1983 ◽  
Vol 59 (1) ◽  
pp. 183-201 ◽  
Author(s):  
P.G. Lord ◽  
A.E. Wheals
Keyword(s):  
Cell Cycle ◽  
Steady State ◽  
Cell Size ◽  
Cycle Time ◽  
Yeast Cells ◽  
Size Difference ◽  
Birth Size ◽  
Daughter Cells ◽  
Alpha Factor ◽  
Determining Factor

The control of cell proliferation under steady-state conditions in the budding yeast, Saccharomyces cerevisiae, is well described by either the tandem or sloppy size control models, both of which suggest that differences in cycle time between individual cells or between parents and daughters is largely due to differences in birth size. These models have been investigated further under conditions in which cell size has not been a rate-determining factor for cell cycle initiation. Two approaches have been used. The first involves the growth of cells in low concentrations of hydroxyurea (HU), which has the effect of prolonging the duration of DNA synthesis. This leads to a lengthening of the budded period, which in turn leads to daughter cells being larger at division than the normal cell cycle initiation size of daughters in steady-state populations. The second approach involves the accumulation of cells at the key control point of the cycle, called start, using the pheromone alpha-factor. Since growth is unaffected, all cells eventually become larger than the volume at which they would normally initiate the cell cycle. The kinetics of proliferation were followed after release from alpha-factor arrest. The results from both approaches were broadly consistent with the predictions of both models. However, abolition of birth-size differences between parents and daughters in the presence of HU did not lead to a complete disappearance of differences in either cycle time or proliferation kinetics. Furthermore, following release from alpha-factor arrest, the rate of cell cycle initiation of parent cells was slower than in steady-state culture and the daughters' cells behaved as if comprising two separate populations. These discrepancies suggest that besides a size difference, there are additional physiological differences between parent and daughter cells.

scholarly journals Fission Yeast Cells Grow Approximately Exponentially

2018 ◽  
Author(s):  
Mary Pickering ◽  
Lauren Nicole Hollis ◽  
Edridge D’Souza ◽  
Nicholas Rhind
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Fission Yeast ◽  
Cell Size ◽  
Exponential Growth ◽  
Cell Biology ◽  
Growth Models ◽  
Growth Period ◽  
Yeast Cells ◽  
Yeast Growth

ABSTRACTHow the rate of cell growth is influenced by cell size is a fundamental question of cell biology. The simple model that cell growth is proportional to cell size, based on the proposition that larger cells have proportionally greater synthetic capacity than smaller cells, leads to the predication that the rate of cell growth increases exponentially with cell size. However, other modes of cell growth, including bilinear growth, have been reported. The distinction between exponential and bilinear growth has been explored in particular detail in the fission yeast Schizosaccharomyces pombe. We have revisited the mode of fission yeast cell growth using high-resolution time-lapse microscopy and find, as previously reported, that these two growth models are difficult to distinguish both because of the similarity in shapes between exponential and bilinear curves over the two-fold change in length of a normal cell cycle and because of the substantial biological and experimental noise inherent to these experiments. Therefore, we contrived to have cells grow more than two fold, by holding them in G2 for up to eight hours. Over this extended growth period, in which cells grow up to 5.5-fold, the two growth models diverge to the point that we can confidently exclude bilinear growth as a general model for fission yeast growth. Although the growth we observe is clearly more complicated than predicted by simple exponential growth, we find that exponential growth is a robust approximation of fission yeast growth, both during an unperturbed cell cycle and during extended periods of growth.

scholarly journals Characterizing non-exponential growth and bimodal cell size distributions in Schizosaccharomyces pombe: an analytical approach

2021 ◽  
Author(s):  
Chen Jia ◽  
Abhyudai Singh ◽  
Ramon Grima
Keyword(s):  
Cell Cycle ◽  
Fission Yeast ◽  
Cell Size ◽  
Control Strategy ◽  
Size Control ◽  
Birth Size ◽  
Size Distributions ◽  
Cell Size Distribution ◽  
A Cell ◽  
Cell Size Control

Unlike many single-celled organisms, the growth of fission yeast cells within a cell cycle is not exponential. It is rather characterized by three distinct phases (elongation, septation and fission), each with a different growth rate. Experiments also show that the distribution of cell size in a lineage is often bimodal, unlike the unimodal distributions measured for the bacterium Escherichia coli. Here we construct a detailed stochastic model of cell size dynamics in fission yeast. The theory leads to analytic expressions for the cell size and the birth size distributions, and explains the origin of bimodality seen in experiments. In particular our theory shows that the left peak in the bimodal distribution is associated with cells in the elongation phase while the right peak is due to cells in the septation and fission phases. We show that the size control strategy, the variability in the added size during a cell cycle and the fraction of time spent in each of the three cell growth phases have a strong bearing on the shape of the cell size distribution. Furthermore we infer all the parameters of our model by matching the theoretical cell size and birth size distributions to those from experimental single cell time-course data for seven different growth conditions. Our method provides a much more accurate means of determining the cell size control strategy (timer, adder or sizer) than the standard method based on the slope of the best linear fit between the birth and division sizes. We also show that the variability in added size and the strength of cell size control of fission yeast depend weakly on the temperature but strongly on the culture medium.

scholarly journals The oscillation of mitotic kinase governs cell cycle latches

2021 ◽  
Author(s):  
Bela Novak ◽  
John J Tyson
Keyword(s):  
Cell Cycle ◽  
Negative Feedback ◽  
Molecular Switches ◽  
Feedback Loops ◽  
Yeast Cells ◽  
Cyclin Dependent Kinases ◽  
Mitotic Kinase ◽  
Daughter Cells ◽  
Negative Feedback Loops ◽  
A Cell

SummaryIn order to transmit a eukaryotic cell’s genome accurately from mother cell to daughter cells, it is essential that the basic events of the cell division cycle (DNA synthesis and mitosis) occur once and only once per cycle, i.e., that a cell progresses irreversibly from G1 to S to G2 to M and back to G1. Irreversible progression through the cell cycle is assured by a sequence of ‘latching’ molecular switches, based on molecular interactions among cyclin-dependent kinases and their auxiliary partners. Positive feedback loops (++ or −−) create bistable switches with latching properties, and negative feedback loops drive progression from one stage to the next. In budding yeast (Saccharomyces cerevisiae) these events are coordinated by double-negative feedback loops between Clb-dependent kinases (Clb1-6) and their antagonists (APC:Cdh1 and Sic1). If the coordinating signal is compromised, either by deletion of Clb1-5 proteins or expression of non-degradable Clb2, then irreversibility is lost and yeast cells exhibit multiple rounds of DNA replication or mitotic exit events (Cdc14 endocycles). Using mathematical modelling of a stripped-down control network, we show how endocycles arise because the switches fail to latch, and the gates swing back and forth by the action of the negative feedback loops.

Variability in individual cell cycles of Saccharomyces cerevisiae

1981 ◽  
Vol 50 (1) ◽  
pp. 361-376 ◽  
Author(s):  
P.G. Lord ◽  
A.E. Wheals
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Proliferation ◽  
Cell Size ◽  
Cycle Time ◽  
Cell Separation ◽  
Deterministic Model ◽  
Time Lapse ◽  
Nuclear Migration ◽  
Daughter Cells ◽  
Bud Emergence

The kinetics of cell proliferation of Saccharomyces cerevisiae were studied at 4 growth rates using time-lapse cinephotomicrography. Cells were grown on media with a high refractive index to reveal greater intracellular detail under the phase-contrast microscope. The morphological cell-cycle events scored were: bud emergence, nuclear migration, nuclear division, onset of cytokinesis and cell separation. Cell size was measured at cell separation and at bud emergence. The daughter-cycle time was always longer than the parent-cycle time mainly due to the large difference in the lengths of the unbudded phases. Parent cells had a shorter budded period than daughter cells. The large variance in daughter-cycle times was accounted for by the large variance in the lengths of the unbudded phase of daughter cells. The duration and variability of the periods in the cyclc from nuclear migration onwards were equivalent for parent and daughter cells. Daughter cells were always smaller than parent cells at division. There was wide variation in cell size at both division and bud emergence. The results indicated that a modified deterministic model could best explain cell proliferation kinetics in yeast. The data were used to evaluate 2 different models. The ‘sloppy size control’ model of Wheals (1981 a) was more consistent with the data than the ‘tandem’ model of Shilo, Shilo & Simchen (1976). The distribution of unbudded periods of daughter cells suggested that there was an additional incompressible period not present in parent cells.

Analysis of the significance of a periodic, cell size-controlled doubling in rates of macromolecular synthesis for the control of balanced exponential growth of fission yeast cells

1979 ◽  
Vol 35 (1) ◽  
pp. 41-51
Author(s):  
A. Barnes ◽  
P. Nurse ◽  
R.S. Fraser
Keyword(s):  
Cell Cycle ◽  
Fission Yeast ◽  
Cell Size ◽  
Exponential Growth ◽  
Messenger Rna ◽  
Rna Synthesis ◽  
Cell Mass ◽  
Yeast Cells ◽  
Periodic Cell ◽  
Threshold Size

Mutant strains of the fission yeast Schizosaccharomyces pombe are available which divide at smaller mean sizes than wild type. Earlier work by the present authors has shown that all these strains double their rates of polyadenylated messenger RNA synthesis as a step once in each cell cycle. The smaller the cell, the later in the cycle is the doubling in rate of synthesis. Strains of all sizes, however, double their synthetic rate when at the same threshold size. We show here that the differences in cell cycle stage of doubling in rate of polyadenylated messenger RNA synthesis are enough to explain the reduced mean steady state polyadenylated messenger RNA contents of the smaller strains. The cell size-related control over doubling in rate of synthesis is also shown to maintain the mean polyadenylated messenger RNA content as a constant proportion of cell mass, irrespective of cell size. This control thus allows cells to maintain balanced exponential growth, even when absolute growth rate per cell is altered by mutation. It is also shown that the concentration of polyadenylated messenger RNA itself could act as a monitor of the threshold size triggering the doubling in rate of synthesis in each cell cycle.

scholarly journals ppGpp is a bacterial cell size regulator

2020 ◽  
Author(s):  
Ferhat Büke ◽  
Jacopo Grilli ◽  
Marco Cosentino Lagomarsino ◽  
Gregory Bokinsky ◽  
Sander Tans
Keyword(s):  
Growth Rate ◽  
Enzyme Activity ◽  
Steady State ◽  
Cell Size ◽  
Growth Control ◽  
Replication Initiation ◽  
Metabolic Enzyme ◽  
Birth Size ◽  
Constant Size ◽  
Metabolic Enzyme Activity

SummaryGrowth and division are central to cell size. Bacteria achieve size homeostasis by dividing when growth has added a constant size since birth, termed the “adder” principle, by unknown mechanisms [1–4]. Growth is well known to be regulated by ppGpp, which controls anything from ribosome production to metabolic enzyme activity and replication initiation, and whose absence or excess can induce the stress response, filamentation, and yield growth-arrested miniature cells [5–8]. These observations raise unresolved questions about the relation between ppGpp and size homeostasis mechanisms during normal exponential growth. Here, to untangle effects of ppGpp and nutrients, we gained control of cellular ppGpp by inducing the synthesis and hydrolysis enzymes RelA and Mesh1. We found that ppGpp not only exerts control over the growth rate, but also over cell division and hence the steady state cell size. The added size responds rapidly to changes in the ppGpp level, aided by transiently accelerated or delayed divisions, and establishes its new constant value while the growth rate still adjusts. Moreover, the magnitude of the added size and resulting steady-state birth size correlate consistently with the ppGpp level, rather than with the growth rate, which results in cells of different size that grow equally fast. Our findings suggest that ppGpp serves as a critical regulator that coordinates cell size and growth control.

scholarly journals Multiple inputs ensure yeast cell size homeostasis during cell cycle progression

2017 ◽  
Author(s):  
Cecilia Garmendia-Torres ◽  
Olivier Tassy ◽  
Audrey Matifas ◽  
Nacho Molina ◽  
Gilles Charvin
Keyword(s):  
Cell Cycle ◽  
Cell Size ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Size Control ◽  
Large Cell ◽  
Yeast Cells ◽  
Cycle Progression ◽  
Size Variability

AbstractCoordination of cell growth and division is essential for proper cell function. In budding yeast, although some molecular mechanisms responsible for cell size control during G1 have been elucidated, the mechanism by which cell size homeostasis is established and maintained throughout the cell cycle remains to be discovered. Here, we developed a new technique based on quantification of histone levels to monitor cell cycle progression in individual yeast cells with unprecedented accuracy. Our analysis establishes the existence of a strong mechanism controlling bud size in G2/M that prevents premature entry into mitosis, and contributes significantly to the overall control of size variability during the cell cycle. While most G1/S regulation mutants do not display any strongly impaired size homeostasis, mutants in which B-type cyclin regulation is altered display large cell-to-cell size variability. Our study thus demonstrates that size homeostasis is not controlled by a G1-specific mechanism but is likely to be an emergent property resulting from the integration of several mechanisms, including the control of cyclin B-Cdk activity, that coordinate cell and bud growth with division.

Tissue economics of hydra: regulation of cell cycle, animal size and development by controlled feeding rates

1977 ◽  
Vol 28 (1) ◽  
pp. 117-132
Author(s):  
J.J. Otto ◽  
R.D. Campbell
Keyword(s):  
Cell Cycle ◽  
Steady State ◽  
Epithelial Cell ◽  
Cycle Time ◽  
Cell Loss ◽  
Tissue Growth ◽  
Tissue Loss ◽  
Feeding Rates ◽  
Cell Cycle Time ◽  
Steady State Condition

Epithelial cell production and epithelial cell loss in 6 different size classes of Hydra attenuata were examined to understand the relationships between growth and morphogenesis. The sizes of adult hydra, the sizes of their buds, and their budding rates are all nearly proportional to the amount of food the hydra eat. Hydra fed at high rates (4-25 Artemia nauplii per day) all have the same epithelial cell cycle time (about 4 days). Budding accounts for most of their cell loss. Hydra fed 4–12 Artemia per day maintain a steady state condition in which tissue loss balances tissue growth. Animals fed 25 Artemia per day are not in a steady state growth condition and change in size. At the lowest feeding rates (0-1 Artemia per day), the epithelial cell cycle time is lengthened to about 16 days. Cell loss from the tentacles accounts for most of the cell loss, and this loss is not completely balanced by growth. As a consequence these animals cease budding and shrink in size.

scholarly journals Constriction rate modulation can drive cell size control and homeostasis inC. crescentus

2018 ◽  
Author(s):  
Ambroise Lambert ◽  
Aster Vanhecke ◽  
Anna Archetti ◽  
Seamus Holden ◽  
Felix Schaber ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Size ◽  
Caulobacter Crescentus ◽  
Size Control ◽  
Time Lapse ◽  
Structured Illumination ◽  
Structured Illumination Microscopy ◽  
Daughter Cells ◽  
Division Site ◽  
Cell Size Control

AbstractRod-shaped bacteria typically grow first via sporadic and dispersed elongation along their lateral walls, then via a combination of zonal elongation and constriction at the division site to form the poles of daughter cells. Although constriction comprises up to half of the cell cycle, its impact on cell size control and homeostasis has rarely been considered. To reveal the roles of cell elongation and constriction in bacterial size regulation during cell division, we captured the shape dynamics ofCaulobacter crescentuswith time-lapse structured illumination microscopy and used molecular markers as cell-cycle landmarks. We perturbed constriction rate using a hyperconstriction mutant or fosfomycin inhibition. We report that constriction rate contributes to both size control and homeostasis, by determining elongation during constriction, and by compensating for variation in pre-constriction elongation on a single-cell basis.

scholarly journals Control of Bacillus subtilis Replication Initiation during Physiological Transitions and Perturbations

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
John T. Sauls ◽  
Sarah E. Cox ◽  
Quynh Do ◽  
Victoria Castillo ◽  
Zulfar Ghulam-Jelani ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bacillus Subtilis ◽  
Steady State ◽  
Single Cell ◽  
Cell Size ◽  
Physiological Parameters ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
E Coli

ABSTRACT Bacillus subtilis and Escherichia coli are evolutionarily divergent model organisms whose analysis has enabled elucidation of fundamental differences between Gram-positive and Gram-negative bacteria, respectively. Despite their differences in cell cycle control at the molecular level, the two organisms follow the same phenomenological principle, known as the adder principle, for cell size homeostasis. We thus asked to what extent B. subtilis and E. coli share common physiological principles in coordinating growth and the cell cycle. We measured physiological parameters of B. subtilis under various steady-state growth conditions with and without translation inhibition at both the population and single-cell levels. These experiments revealed core physiological principles shared between B. subtilis and E. coli. Specifically, both organisms maintain an invariant cell size per replication origin at initiation, under all steady-state conditions, and even during nutrient shifts at the single-cell level. Furthermore, the two organisms also inherit the same “hierarchy” of physiological parameters. On the basis of these findings, we suggest that the basic principles of coordination between growth and the cell cycle in bacteria may have been established early in evolutionary history. IMPORTANCE High-throughput, quantitative approaches have enabled the discovery of fundamental principles describing bacterial physiology. These principles provide a foundation for predicting the behavior of biological systems, a widely held aspiration. However, these approaches are often exclusively applied to the best-known model organism, E. coli. In this report, we investigate to what extent quantitative principles discovered in Gram-negative E. coli are applicable to Gram-positive B. subtilis. We found that these two extremely divergent bacterial species employ deeply similar strategies in order to coordinate growth, cell size, and the cell cycle. These similarities mean that the quantitative physiological principles described here can likely provide a beachhead for others who wish to understand additional, less-studied prokaryotes.

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