scholarly journals Endogenous Replication Stress in Mother Cells Leads to Quiescence of Daughter Cells

Cell Reports ◽  
2017 ◽  
Vol 19 (7) ◽  
pp. 1351-1364 ◽  
Author(s):  
Mansi Arora ◽  
Justin Moser ◽  
Harsha Phadke ◽  
Ashik Akbar Basha ◽  
Sabrina L. Spencer
Keyword(s):  
Replication Stress ◽  
Daughter Cells ◽  
Mother Cells

scholarly journals The dynamic equilibrium of nascent and parental MCMs safeguards replicating genomes

2019 ◽  
Author(s):  
Hana Sedlackova ◽  
Maj-Britt Rask ◽  
Rajat Gupta ◽  
Chunaram Choudhary ◽  
Kumar Somyajit ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Dynamic Equilibrium ◽  
Genome Instability ◽  
Replication Stress ◽  
Minichromosome Maintenance ◽  
Daughter Cells ◽  
Mild Reduction ◽  
Dividing Cells ◽  
High Level ◽  
Mother Cells

The MCM2-7 (minichromosome maintenance) protein complex is a DNA unwinding motor required for the eukaryotic genome duplication1. Although a huge excess of MCM2-7 is loaded onto chromatin in G1 phase to form pre-replication complexes (pre-RCs), only 5-10 percent are converted into a productive CDC45-MCM-GINS (CMG) helicase in S phase – a perplexing phenomenon often referred to as the ‘MCM paradox’2. Remaining pre-RCs stay dormant but can be activated under replication stress (RS)3. Remarkably, even a mild reduction in MCM pool results in genome instability4, 5, underscoring the critical requirement for high-level MCM maintenance to safeguard genome integrity across generations of dividing cells. How this is achieved remains unknown. Here, we show that for daughter cells to sustain error-free DNA replication, their mothers build up a stable nuclear pool of MCMs both by recycling of chromatin-bound MCMs (referred to as parental pool) and synthesizing new MCMs (referred to as nascent pool). We find that MCMBP, a distant MCM paralog6, ensures the influx of nascent MCMs to the declining recycled pool, and thereby sustains critical levels of MCMs. MCMBP promotes nuclear translocation of nascent MCM3-7 (but not MCM2), which averts accelerated MCM proteolysis in the cytoplasm, and thereby fosters assembly of licensing-competent nascent MCM2-7 units. Consequently, lack of MCMBP leads to reduction of nascent MCM3-7 subunits in mother cells, which translates to poor MCM inheritance and grossly reduced pre-RCs formation in daughter cells. Unexpectedly, whereas the pre-RC paucity caused by MCMBP deficiency does not alter the overall bulk DNA synthesis, it escalates the speed and asymmetry of individual replisomes. This in turn increases endogenous replication stress and renders cells hypersensitive to replication perturbations. Thus, we propose that surplus of MCMs is required to safeguard replicating genomes by modulating physiological dynamics of fork progression through chromatin marked by licensed but inactive MCM2-7 complexes.

scholarly journals Low Replicative Stress Triggers Cell-Type Specific Inheritable Advanced Replication Timing

2021 ◽  
Vol 22 (9) ◽  
pp. 4959
Author(s):  
Lilas Courtot ◽  
Elodie Bournique ◽  
Chrystelle Maric ◽  
Laure Guitton-Sert ◽  
Miguel Madrid-Mencía ◽  
...  
Keyword(s):  
Replication Timing ◽  
Replication Stress ◽  
Chromatin Accessibility ◽  
Cell Type ◽  
Replicative Stress ◽  
Daughter Cells ◽  
Origin Activation ◽  
Cell Type Specific ◽  
Cellular Identity ◽  
Dna Replication Timing

DNA replication timing (RT), reflecting the temporal order of origin activation, is known as a robust and conserved cell-type specific process. Upon low replication stress, the slowing of replication forks induces well-documented RT delays associated to genetic instability, but it can also generate RT advances that are still uncharacterized. In order to characterize these advanced initiation events, we monitored the whole genome RT from six independent human cell lines treated with low doses of aphidicolin. We report that RT advances are cell-type-specific and involve large heterochromatin domains. Importantly, we found that some major late to early RT advances can be inherited by the unstressed next-cellular generation, which is a unique process that correlates with enhanced chromatin accessibility, as well as modified replication origin landscape and gene expression in daughter cells. Collectively, this work highlights how low replication stress may impact cellular identity by RT advances events at a subset of chromosomal domains.

scholarly journals Daughter cells of Saccharomyces cerevisiae from old mothers display a reduced life span.

1994 ◽  
Vol 127 (6) ◽  
pp. 1985-1993 ◽  
Author(s):  
B K Kennedy ◽  
N R Austriaco ◽  
L Guarente
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Life Span ◽  
Daughter Cell ◽  
Young Mothers ◽  
Young Mother ◽  
Yeast Saccharomyces Cerevisiae ◽  
Daughter Cells ◽  
Per Se ◽  
Mother Cells ◽  
Maximum Occurrence

The yeast Saccharomyces cerevisiae typically divides asymmetrically to give a large mother cell and a smaller daughter cell. As mother cells become old, they enlarge and produce daughter cells that are larger than daughters derived from young mother cells. We found that occasional daughter cells were indistinguishable in size from their mothers, giving rise to a symmetric division. The frequency of symmetric divisions became greater as mother cells aged and reached a maximum occurrence of 30% in mothers undergoing their last cell division. Symmetric divisions occurred similarly in rad9 and ste12 mutants. Strikingly, daughters from old mothers, whether they arose from symmetric divisions or not, displayed reduced life spans relative to daughters from young mothers. Because daughters from old mothers were larger than daughters from young mothers, we investigated whether an increased size per se shortened life span and found that it did not. These findings are consistent with a model for aging that invokes a senescence substance which accumulates in old mother cells and is inherited by their daughters.

scholarly journals FACT and Ash1 promote long-range and bidirectional nucleosome eviction at the HO promoter

2020 ◽  
Vol 48 (19) ◽  
pp. 10877-10889 ◽  
Author(s):  
Yaxin Yu ◽  
Robert M Yarrington ◽  
David J Stillman
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Regulatory System ◽  
High Concentration ◽  
Long Distance ◽  
Mothers And Daughters ◽  
Daughter Cells ◽  
Dna Binding Factors ◽  
Mother Cells ◽  
Promoter Recruitment ◽  
Ho Gene

Abstract The Saccharomyces cerevisiae HO gene is a model regulatory system with complex transcriptional regulation. Budding yeast divide asymmetrically and HO is expressed only in mother cells where a nucleosome eviction cascade along the promoter during the cell cycle enables activation. HO expression in daughter cells is inhibited by high concentration of Ash1 in daughters. To understand how Ash1 represses transcription, we used a myo4 mutation which boosts Ash1 accumulation in both mothers and daughters and show that Ash1 inhibits promoter recruitment of SWI/SNF and Gcn5. We show Ash1 is also required for the efficient nucleosome repopulation that occurs after eviction, and the strongest effects of Ash1 are seen when Ash1 has been degraded and at promoter locations distant from where Ash1 bound. Additionally, we defined a specific nucleosome/nucleosome-depleted region structure that restricts HO activation to one of two paralogous DNA-binding factors. We also show that nucleosome eviction occurs bidirectionally over a large distance. Significantly, eviction of the more distant nucleosomes is dependent upon the FACT histone chaperone, and FACT is recruited to these regions when eviction is beginning. These last observations, along with ChIP experiments involving the SBF factor, suggest a long-distance loop transiently forms at the HO promoter.

scholarly journals Cell cycle phases in the unequal mother/daughter cell cycles of Saccharomyces cerevisiae.

1984 ◽  
Vol 4 (11) ◽  
pp. 2529-2531 ◽  
Author(s):  
B J Brewer ◽  
E Chlebowicz-Sledziewska ◽  
W L Fangman
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Cycle Phase ◽  
Cell Cycle Time ◽  
Yeast Saccharomyces Cerevisiae ◽  
Cell Cycles ◽  
Daughter Cells ◽  
Mother And Daughter ◽  
Cell Cycle Phases ◽  
Mother Cells

During cell division in the yeast Saccharomyces cerevisiae mother cells produce buds (daughter cells) which are smaller and have longer cell cycles. We performed experiments to compare the lengths of cell cycle phases in mothers and daughters. As anticipated from earlier indirect observations, the longer cell cycle time of daughter cells is accounted for by a longer G1 interval. The S-phase and the G2-phase are of the same duration in mother and daughter cells. An analysis of five isogenic strains shows that cell cycle phase lengths are independent of cell ploidy and mating type.

scholarly journals Key events during the transition from rapid growth to quiescence in budding yeast require posttranscriptional regulators

2013 ◽  
Vol 24 (23) ◽  
pp. 3697-3709 ◽  
Author(s):  
Lihong Li ◽  
Shawna Miles ◽  
Zephan Melville ◽  
Amalthiya Prasad ◽  
Graham Bradley ◽  
...  
Keyword(s):  
Cell Walls ◽  
Posttranscriptional Regulation ◽  
Cell Formation ◽  
Cell Types ◽  
G1 Arrest ◽  
Quiescent State ◽  
Diauxic Shift ◽  
Cell Wall Assembly ◽  
Daughter Cells ◽  
Mother Cells

Yeast that naturally exhaust the glucose from their environment differentiate into three distinct cell types distinguishable by flow cytometry. Among these is a quiescent (Q) population, which is so named because of its uniform but readily reversed G1 arrest, its fortified cell walls, heat tolerance, and longevity. Daughter cells predominate in Q-cell populations and are the longest lived. The events that differentiate Q cells from nonquiescent (nonQ) cells are initiated within hours of the diauxic shift, when cells have scavenged all the glucose from the media. These include highly asymmetric cell divisions, which give rise to very small daughter cells. These daughters modify their cell walls by Sed1- and Ecm33-dependent and dithiothreitol-sensitive mechanisms that enhance Q-cell thermotolerance. Ssd1 speeds Q-cell wall assembly and enables mother cells to enter this state. Ssd1 and the related mRNA-binding protein Mpt5 play critical overlapping roles in Q-cell formation and longevity. These proteins deliver mRNAs to P-bodies, and at least one P-body component, Lsm1, also plays a unique role in Q-cell longevity. Cells lacking Lsm1 and Ssd1 or Mpt5 lose viability under these conditions and fail to enter the quiescent state. We conclude that posttranscriptional regulation of mRNAs plays a crucial role in the transition in and out of quiescence.

scholarly journals Epigenetic Regulation of Plant Gametophyte Development

2019 ◽  
Vol 20 (12) ◽  
pp. 3051 ◽  
Author(s):  
Vasily V. Ashapkin ◽  
Lyudmila I. Kutueva ◽  
Nadezhda I. Aleksandrushkina ◽  
Boris F. Vanyushin
Keyword(s):  
Mother Cell ◽  
Female Gametophyte ◽  
Male Gametophyte ◽  
Endosperm Development ◽  
Epigenetic Changes ◽  
Gametophyte Development ◽  
Daughter Cells ◽  
Second Stage ◽  
Somatic Tissues ◽  
Mother Cells

Unlike in animals, the reproductive lineage cells in plants differentiate from within somatic tissues late in development to produce a specific haploid generation of the life cycle—male and female gametophytes. In flowering plants, the male gametophyte develops within the anthers and the female gametophyte—within the ovule. Both gametophytes consist of only a few cells. There are two major stages of gametophyte development—meiotic and post-meiotic. In the first stage, sporocyte mother cells differentiate within the anther (pollen mother cell) and the ovule (megaspore mother cell). These sporocyte mother cells undergo two meiotic divisions to produce four haploid daughter cells—male spores (microspores) and female spores (megaspores). In the second stage, the haploid spore cells undergo few asymmetric haploid mitotic divisions to produce the 3-cell male or 7-cell female gametophyte. Both stages of gametophyte development involve extensive epigenetic reprogramming, including siRNA dependent changes in DNA methylation and chromatin restructuring. This intricate mosaic of epigenetic changes determines, to a great extent, embryo and endosperm development in the future sporophyte generation.

scholarly journals Myosin-driven peroxisome partitioning in S. cerevisiae

2009 ◽  
Vol 186 (4) ◽  
pp. 541-554 ◽  
Author(s):  
Andrei Fagarasanu ◽  
Fred D. Mast ◽  
Barbara Knoblach ◽  
Yui Jin ◽  
Matthew J. Brunner ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Molecular Motors ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Class V ◽  
Daughter Cells ◽  
Mother And Daughter ◽  
Specific Receptors ◽  
Cycle Dependent ◽  
Mother Cells

In Saccharomyces cerevisiae, the class V myosin motor Myo2p propels the movement of most organelles. We recently identified Inp2p as the peroxisome-specific receptor for Myo2p. In this study, we delineate the region of Myo2p devoted to binding peroxisomes. Using mutants of Myo2p specifically impaired in peroxisome binding, we dissect cell cycle–dependent and peroxisome partitioning–dependent mechanisms of Inp2p regulation. We find that although total Inp2p levels oscillate with the cell cycle, Inp2p levels on individual peroxisomes are controlled by peroxisome inheritance, as Inp2p aberrantly accumulates and decorates all peroxisomes in mother cells when peroxisome partitioning is abolished. We also find that Inp2p is a phosphoprotein whose level of phosphorylation is coupled to the cell cycle irrespective of peroxisome positioning in the cell. Our findings demonstrate that both organelle positioning and cell cycle progression control the levels of organelle-specific receptors for molecular motors to ultimately achieve an equidistribution of compartments between mother and daughter cells.

scholarly journals Characterization of the Saccharomyces Golgi complex through the cell cycle by immunoelectron microscopy.

1992 ◽  
Vol 3 (7) ◽  
pp. 789-803 ◽  
Author(s):  
D Preuss ◽  
J Mulholland ◽  
A Franzusoff ◽  
N Segev ◽  
D Botstein
Keyword(s):  
Cell Cycle ◽  
Immunoelectron Microscopy ◽  
Early Stage ◽  
Secretory Vesicles ◽  
Wild Type ◽  
Daughter Cells ◽  
Bud Emergence ◽  
Membrane Compartments ◽  
Mother Cells

The membrane compartments responsible for Golgi functions in wild-type Saccharomyces cerevisiae were identified and characterized by immunoelectron microscopy. Using improved fixation methods, Golgi compartments were identified by labeling with antibodies specific for alpha 1-6 mannose linkages, the Sec7 protein, or the Ypt1 protein. The compartments labeled by each of these antibodies appear as disk-like structures that are apparently surrounded by small vesicles. Yeast Golgi typically are seen as single, isolated cisternae, generally not arranged into parallel stacks. The location of the Golgi structures was monitored by immunoelectron microscopy through the yeast cell cycle. Several Golgi compartments, apparently randomly distributed, were always observed in mother cells. During the initiation of new daughter cells, additional Golgi structures cluster just below the site of bud emergence. These Golgi enter daughter cells at an early stage, raising the possibility that much of the bud's growth might be due to secretory vesicles formed as well as consumed entirely within the daughter. During cytokinesis, the Golgi compartments are concentrated near the site of cell wall synthesis. Clustering of Golgi both at the site of bud formation and at the cell septum suggests that these organelles might be directed toward sites of rapid cell surface growth.

scholarly journals Cdc42 GTPase Activating Proteins (GAPs) Maintain Generational Inheritance of Cell Polarity and Cell Shape in Fission Yeast

2020 ◽  
Author(s):  
Marbelys Rodriguez Pino ◽  
Illyce Nuñez ◽  
Chuan Chen ◽  
Maitreyi E. Das ◽  
David J. Wiley ◽  
...  
Keyword(s):  
Computational Models ◽  
Protein Localization ◽  
Small Gtpase ◽  
Growth Patterns ◽  
Unequal Distribution ◽  
Oscillatory Dynamics ◽  
Daughter Cells ◽  
Gtpase Activating Proteins ◽  
Growth Activation ◽  
Mother Cells

AbstractThe highly conserved small GTPase Cdc42 regulates polarized cell growth and morphogenesis from yeast to humans. We previously reported that Cdc42 activation exhibits oscillatory dynamics in Schizosaccharomyces pombe cells. Mathematical modeling suggests that this dynamic behavior enables a variety of symmetric and asymmetric Cdc42 distributions to coexist in cell populations. For individual wild type cells, however, growth follows a stereotypical pattern where Cdc42 distribution is initially asymmetrical in young daughter cells and becomes more symmetrical as cell volume increases, enabling bipolar growth activation. To explore whether different states of Cdc42 activation are possible in a biological context, we examined S. pombe rga4Δ mutant cells, lacking the Cdc42 GTPase activating protein (GAP) Rga4. We found that monopolar rga4Δ mother cells divide asymmetrically leading to the emergence of both symmetric and asymmetric Cdc42 distributions in rga4Δ daughter cells. Using genetic screening approaches to identify mutants that alter the rga4Δ phenotype, we tested the predictions of different computational models that reproduce the unequal fate of daughter cells. We found experimentally that the unequal distribution of active Cdc42 GTPase in daughter cells is consistent with an unequal inheritance of another Cdc42 GAP, Rga6, in the two daughter cells. Our findings highlight the crucial role of Cdc42 GAP protein localization in determining the morphological fate of cell progeny and ensuring consistent Cdc42 activation and growth patterns across generations.

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