scholarly journals Size-independent mRNA synthesis and chromatin-based partitioning mechanisms generate and maintain constant amounts of protein per cell

2020 ◽  
Author(s):  
Matthew P. Swaffer ◽  
Devon Chandler-Brown ◽  
Maurice Langhinrichs ◽  
Georgi Marinov ◽  
William Greenleaf ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Expression ◽  
Cell Size ◽  
Control Cell ◽  
Chromatin Binding ◽  
Mrna Synthesis ◽  
Genome Content ◽  
Histone Synthesis ◽  
Independent Protein ◽  
Budding Yeast Cell Cycle

SummaryCell size and biosynthesis are inextricably linked. As cells grow, total protein synthesis increases in proportion to cell size so that protein concentrations remain constant. As an exception, the budding yeast cell-cycle inhibitor Whi5 is synthesized in a constant amount per cell cycle, so that it is diluted in large cells to trigger division. Here, we show that this size-independent expression of Whi5 results from size-independent transcription. A screen for similar genes identified histones as the major class of size-independent transcripts during the cell cycle, consistent with histone synthesis being coupled to genome content rather than cell size. However, during asymmetric division size-independent transcription is insufficient for size-independent protein expression and chromatin-binding ensures equal amounts of protein are partitioned to unequally sized cells to maintain size-independent protein amounts. Thus, specific transcriptional and partitioning mechanisms determine size-independent protein expression to control cell size.

scholarly journals PP2ARts1 is a master regulator of pathways that control cell size

2014 ◽  
Vol 204 (3) ◽  
pp. 359-376 ◽  
Author(s):  
Jessica Zapata ◽  
Noah Dephoure ◽  
Tracy MacDonough ◽  
Yaxin Yu ◽  
Emily J. Parnell ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Cell Size ◽  
Control Cell ◽  
Size Control ◽  
Regulatory Subunit ◽  
Delay Cell ◽  
Cell Cycle Entry ◽  
G1 Cyclin

Cell size checkpoints ensure that passage through G1 and mitosis occurs only when sufficient growth has occurred. The mechanisms by which these checkpoints work are largely unknown. PP2A associated with the Rts1 regulatory subunit (PP2ARts1) is required for cell size control in budding yeast, but the relevant targets are unknown. In this paper, we used quantitative proteome-wide mass spectrometry to identify proteins controlled by PP2ARts1. This revealed that PP2ARts1 controls the two key checkpoint pathways thought to regulate the cell cycle in response to cell growth. To investigate the role of PP2ARts1 in these pathways, we focused on the Ace2 transcription factor, which is thought to delay cell cycle entry by repressing transcription of the G1 cyclin CLN3. Diverse experiments suggest that PP2ARts1 promotes cell cycle entry by inhibiting the repressor functions of Ace2. We hypothesize that control of Ace2 by PP2ARts1 plays a role in mechanisms that link G1 cyclin accumulation to cell growth.

scholarly journals A hierarchical transcriptional network activates specific CDK inhibitors that regulate G2 to control cell size and number in Arabidopsis

2021 ◽  
Author(s):  
Yuji Nomoto ◽  
Hirotomo Takatsuka ◽  
Kesuke Yamada ◽  
Toshiya Suzuki ◽  
Takamasa Suzuki ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Cell Size ◽  
Cell Biology ◽  
Cell Cycle Progression ◽  
Transcriptional Regulatory Network ◽  
Critical Role ◽  
Control Cell ◽  
Transcriptional Network ◽  
Phase Cell

How cell size and number are determined during organ development remains a fundamental question in cell biology. Here, we identified a GRAS family transcription factor, called SCARECROW-LIKE28 (SCL28), with a critical role in determining cell size in Arabidopsis. SCL28 is part of a transcriptional regulatory network downstream of the central MYB3Rs that regulate G2 to M phase cell cycle transition. We show that SCL28 forms a dimer with the AP2-type transcription factor, AtSMOS1, which defines the specificity for promoter binding and directly activates transcription of a specific set of SIAMESE-RELATED (SMR) family genes, encoding plant-specific inhibitors of cyclin-dependent kinases and thus inhibiting cell cycle progression at G2 and promoting the onset of endoreplication. Through this dose-dependent regulation of SMR transcription, SCL28 quantitatively sets the balance between cell size and number without dramatically changing final organ size. We propose that this hierarchical transcriptional network constitutes a cell cycle regulatory mechanism that allows to adjust cell size and number to attain robust organ growth.

Cell size modulation by CDC25 and RAS2 genes in Saccharomyces cerevisiae

1989 ◽  
Vol 9 (6) ◽  
pp. 2715-2723
Author(s):  
M D Baroni ◽  
E Martegani ◽  
P Monti ◽  
L Alberghina
Keyword(s):  
Cell Cycle ◽  
Cell Size ◽  
Culture Media ◽  
Control Cell ◽  
Cell Mass ◽  
Growth Conditions ◽  
Growth Defect ◽  
Permissive Temperature ◽  
Wild Type ◽  
Nutritional Conditions

A detailed kinetic analysis of the cell cycle of cdc25-1, RAS2Val-19, or cdc25-1/RAS2Val-19 mutants during exponential growth is presented. At the permissive temperature (24 degrees C), cdc25-1 cells show a longer G1/unbudded phase of the cell cycle and have a smaller critical cell size required for budding without changing the growth rate in comparison to an isogenic wild type. The RAS2Val-19 mutation efficiently suppresses the ts growth defect of the cdc25-1 mutant at 36 degrees C and the increase of G1 phase at 24 degrees C. Moreover, it causes a marked increase of the critical cell mass required to enter into a new cell division cycle compared with that of the wild type. Since the critical cell mass is physiologically modulated by nutritional conditions, we have also studied the behavior of these mutants in different media. The increase in cell size caused by the RAS2Val-19 mutation is evident in all tested growth conditions, while the effect of cdc25-1 is apparently more pronounced in rich culture media. CDC25 and RAS2 gene products have been showed to control cell growth by regulating the cyclic AMP metabolic pathway. Experimental evidence reported herein suggests that the modulation of the critical cell size by CDC25 and RAS2 may involve adenylate cyclase.

scholarly journals Dilution and titration of cell-cycle regulators may control cell size in budding yeast

2018 ◽  
Vol 14 (10) ◽  
pp. e1006548 ◽  
Author(s):  
Frank S. Heldt ◽  
Reece Lunstone ◽  
John J. Tyson ◽  
Béla Novák
Keyword(s):  
Cell Cycle ◽  
Cell Size ◽  
Budding Yeast ◽  
Control Cell ◽  
Cell Cycle Regulators

scholarly journals Integrated biphasic growth rate, gene expression, and cell-size homeostasis behaviour of singleB. subtiliscells

2019 ◽  
Author(s):  
Niclas Nordholt ◽  
Johan H. van Heerden ◽  
Frank J. Bruggeman
Keyword(s):  
Cell Cycle ◽  
Growth Rate ◽  
Cell Division ◽  
Protein Expression ◽  
Cell Size ◽  
Cell Cycle Progression ◽  
Bacterial Cells ◽  
Cycle Progression ◽  
Average Cell ◽  
Cycle Dependent

ABSTRACTThe growth rate of single bacterial cells is continuously disturbed by random fluctuations in biosynthesis rates and by deterministic cell-cycle events, such as division, genome duplication, and septum formation. It is not understood whether, and how, bacteria reject these disturbances. Here we quantified growth and constitutive protein expression dynamics of singleBacillus subtiliscells, as a function of cell-cycle-progression. Variation in birth size and growth rate, resulting from unequal cell division, is largely compensated for when cells divide again. We analysed the cell-cycle-dynamics of these compensations and found that both growth and protein expression exhibited biphasic behaviour. During a first phase of variable duration, the absolute rates were approximately constant and cells behaved as sizers. In the second phase, rates increased and growth behaviour exhibited characteristics of a timer-strategy. This work shows how cell-cycle-dependent rate adjustments of biosynthesis and growth are integrated to compensate for physio-logical disturbances caused by cell division.IMPORTANCEUnder constant conditions, bacterial populations can maintain a fixed average cell size and constant exponential growth rate. At the single cell-level, however, cell-division can cause significant physiological perturbations, requiring compensatory mechanisms to restore the growth-related characteristics of individual cells toward that of the average cell. Currently, there is still a major gap in our understanding of the dynamics of these mechanisms, i.e. how adjustments in growth, metabolism and biosynthesis are integrated during the bacterial cell-cycle to compensate the disturbances caused by cell division. Here we quantify growth and constitutive protein expression in individual bacterial cells at sub-cell-cycle resolution. Significantly, both growth and protein production rates display structured and coordinated cell-cycle-dependent dynamics. These patterns reveal the dynamics of growth rate and size compensations during cell-cycle progression. Our findings provide a dynamic cell-cycle perspective that offers novel avenues for the interpretation of physiological processes that underlie cellular homeostasis in bacteria.

scholarly journals CDK control pathways integrate cell size and ploidy information to control cell division

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
James Oliver Patterson ◽  
Souradeep Basu ◽  
Paul Rees ◽  
Paul Nurse
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Size ◽  
Control Cell ◽  
Size Information ◽  
Inhibitory Tyrosine Phosphorylation ◽  
Dependent Inhibition ◽  
Control Cell Division ◽  
Diploid Cells

Maintenance of cell size homeostasis is a property that is conserved throughout eukaryotes. Cell size homeostasis is brought about by the co-ordination of cell division with cell growth, and requires restriction of smaller cells from undergoing mitosis and cell division, whilst allowing larger cells to do so. Cyclin-CDK is the fundamental driver of mitosis and therefore ultimately ensures size homeostasis. Here we dissect determinants of CDK activity in vivo to investigate how cell size information is processed by the cell cycle network in fission yeast. We develop a high-throughput single-cell assay system of CDK activity in vivo and show that inhibitory tyrosine phosphorylation of CDK encodes cell size information, with the phosphatase PP2A aiding to set a size threshold for division. CDK inhibitory phosphorylation works synergistically with PP2A to prevent mitosis in smaller cells. Finally, we find that diploid cells of equivalent size to haploid cells exhibit lower CDK activity in response to equal cyclin-CDK enzyme concentrations, suggesting that CDK activity is reduced by increased DNA levels. Therefore, scaling of cyclin-CDK levels with cell size, CDK inhibitory phosphorylation, PP2A, and DNA-dependent inhibition of CDK activity, all inform the cell cycle network of cell size, thus contributing to cell-size homeostasis.

scholarly journals Cell size modulation by CDC25 and RAS2 genes in Saccharomyces cerevisiae.

1989 ◽  
Vol 9 (6) ◽  
pp. 2715-2723 ◽  
Author(s):  
M D Baroni ◽  
E Martegani ◽  
P Monti ◽  
L Alberghina
Keyword(s):  
Cell Cycle ◽  
Cell Size ◽  
Culture Media ◽  
Control Cell ◽  
Cell Mass ◽  
Growth Conditions ◽  
Growth Defect ◽  
Permissive Temperature ◽  
Wild Type ◽  
Nutritional Conditions

A detailed kinetic analysis of the cell cycle of cdc25-1, RAS2Val-19, or cdc25-1/RAS2Val-19 mutants during exponential growth is presented. At the permissive temperature (24 degrees C), cdc25-1 cells show a longer G1/unbudded phase of the cell cycle and have a smaller critical cell size required for budding without changing the growth rate in comparison to an isogenic wild type. The RAS2Val-19 mutation efficiently suppresses the ts growth defect of the cdc25-1 mutant at 36 degrees C and the increase of G1 phase at 24 degrees C. Moreover, it causes a marked increase of the critical cell mass required to enter into a new cell division cycle compared with that of the wild type. Since the critical cell mass is physiologically modulated by nutritional conditions, we have also studied the behavior of these mutants in different media. The increase in cell size caused by the RAS2Val-19 mutation is evident in all tested growth conditions, while the effect of cdc25-1 is apparently more pronounced in rich culture media. CDC25 and RAS2 gene products have been showed to control cell growth by regulating the cyclic AMP metabolic pathway. Experimental evidence reported herein suggests that the modulation of the critical cell size by CDC25 and RAS2 may involve adenylate cyclase.

scholarly journals Dilution and titration of cell-cycle regulators may control cell size in budding yeast

2018 ◽  
Author(s):  
Frank S. Heldt ◽  
Reece Lunstone ◽  
John J. Tyson ◽  
Béla Novák
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Cell Size ◽  
Cell Cycle Progression ◽  
Budding Yeast ◽  
Control Cell ◽  
Gene Copy Number ◽  
Size Control ◽  
Gene Copy ◽  
Cell Cycle Regulators

AbstractThe size of a cell sets the scale for all biochemical processes within it, thereby affecting cellular fitness and survival. Hence, cell size needs to be kept within certain limits and relatively constant over multiple generations. However, how cells measure their size and use this information to regulate growth and division remains controversial. Here, we present two mechanistic mathematical models of the budding yeast (S. cerevisiae) cell cycle to investigate competing hypotheses on size control: inhibitor dilution and titration of nuclear sites. Our results suggest that an inhibitor-dilution mechanism, in which cell growth dilutes the transcriptional inhibitor Whi5 against the constant activator Cln3, can facilitate size homeostasis. This is achieved by utilising a positive feedback loop to establish a fixed size threshold for the START transition, which efficiently couples cell growth to cell cycle progression. Yet, we show that inhibitor dilution cannot reproduce the size of mutants that alter the cell’s overall ploidy and WHI5 gene copy number. By contrast, size control through titration of Cln3 against a constant number of genomic binding sites for the transcription factor SBF recapitulates both size homeostasis and the size of these mutant strains. Moreover, this model produces an imperfect ‘sizer’ behaviour in G1 and a ‘timer’ in S/G2/M, which combine to yield an ‘adder’ over the whole cell cycle; an observation recently made in experiments. Hence, our model connects these phenomenological data with the molecular details of the cell cycle, providing a systems-level perspective of budding yeast size control.

Sign in / Sign up

Export Citation Format

Share Document