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 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 Positive Effects of Omega - 3 Fatty Acids on a group of Metabolic Enzyme Activity in Rat Lİver

2016 ◽  
Vol 5 (2) ◽  
pp. 62-68
Author(s):  
Burak Gülcen ◽  
Emrah Özcan ◽  
Murat Abdulgani Kuş ◽  
Ömür Karaca Saygılı ◽  
Dilara Kaman ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Enzyme Activity ◽  
Rat Liver ◽  
Metabolic Enzyme ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Positive Effects ◽  
Metabolic Enzyme Activity

scholarly journals Coordination between E. coli Cell Size and Cell Cycle Mediated by DnaA

2020 ◽  
Author(s):  
Qing Zhang ◽  
Zhichao Zhang ◽  
Hualin Shi
Keyword(s):  
Cell Cycle ◽  
Growth Rate ◽  
Dna Replication ◽  
Cell Size ◽  
Doubling Time ◽  
Cell Mass ◽  
Replication Initiation ◽  
General Relationship ◽  
E Coli ◽  
Regulatory Processes

Sixty years ago, bacterial cell size was found as an exponential function of growth rate. Fifty years ago, a more general relationship was proposed, in which the cell mass was equal to the initiation mass multiplied by the ratio of the total time of the C and D periods to the doubling time. This relationship has recently been experimentally confirmed by perturbing doubling time, C period, D period or the initiation mass. However, the underlying molecular mechanism remains unclear. Here, we developed a mechanistic and kinetic model to describe how the initiator protein DnaA mediates the initiation of DNA replication in E. coli. In the model, we introduced an initiation probability function involving competitive binding of DnaA-ATP (active) and DnaA-ADP (inactive) at replication origin to determine the initiation of replication. In addition, we considered RNAP availability, ppGpp inhibition, DnaA autorepression, DnaA titration by chromosomal sites, hydrolysis of DnaA-ATP along with DNA replication, reactivation of DnaA-ADP and established a kinetic description of these DnaA regulatory processes. We simulated DnaA kinetics and obtained a self-consistent cell size and a regular DnaA oscillation coordinated with the cell cycle at steady state. The relationship between the cell size obtained by the simulation and the growth rate, C period, D period or initiation mass reproduces the results of the experiment. This model also predicts how the number of DnaA and the initiation mass vary with the perturbation parameters (including those reflecting the mutation or interference of DnaA regulatory processes), which is comparable to experimental data. The results suggest that the regulatory mechanisms of DnaA level and activity are associated with the invariance of initiation mass and the cell size general relationship for matching frequencies of replication initiation and cell division. This study may provide clues for concerted control of cell size and cell cycle in synthetic biology.

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