Tributyltin induces cell cycle arrest at G1 phase in the yeast &lt;i&gt;Saccharomyces cerevisiae&lt;/i&gt;

Sekito, Takayuki; Sugimoto, Naoko; Ishimoto, Masaya; Kawano‐Kawada, Miyuki; Akiyama, Koichi; Nishimoto, Sogo; Sugahara, Takuya; Kakinuma, Yoshihiko

doi:10.2131/jts.39.311

Cited by 5 publications

(3 citation statements)

References 25 publications

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“…To further study the dependence of the MAPK pathway on IP-1-induced cell death, we induced cell cycle arrest of MATα cells using cell cycle inhibitors that do not target the pheromone pathway, but do activate the MAPK pathway. Specifically, we used nocodazole to synchronize cells in the M phase and activate the MAPK pathway ( Hayne et al, 2000 ) and tributyltin (TBT) to shift the cell cycle arrest induced by nocodazole to G 0 /G 1 ( Sekito et al, 2014 ) in MATα cells, which do not express the pheromone receptor (see section “Materials and Methods”). We validated the inhibition of growth of MATα cells treated with each cell cycle inhibitor and we included MATa cells in these experiments as positive controls for IP-1 cytotoxicity (see Supplementary Figure S6 ).…”

Section: Resultsmentioning

confidence: 99%

“…Cells were grown in 4 mL YPD at 30°C at 250 rpm in constant agitation for 16 h; they were then diluted with YPD to an optical density of 0.12 at 600 nm. The culture was grown to an optical density of 0.4 and then treated with 15 μg/mL nocodazole for 2 h. Cells treated with nocodazole were arrested in G 0 /G 1 phase using 5 μM TBT (tributyltin) for 2 h; it has been reported that under such conditions over 90% of the population was in G 1 /G 0 phase ( Sekito et al, 2014 ). Samples were taken for analysis of cell cycle and viability as described in Sections “FUN1 Viability Assay” and “Cell Cycle Analysis.”…”

Section: Methodsmentioning

confidence: 99%

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An Antimicrobial Peptide Induces FIG1-Dependent Cell Death During Cell Cycle Arrest in Yeast

et al. 2018

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Although most antibiotics act on cells that are actively dividing and non-dividing cells such as in microbe sporulation or cancer stem cells represent a new paradigm for the control of disease. In addition to their relevance to health, such antibiotics may promote our understanding of the relationship between the cell cycle and cell death. No antibiotic specifically acting on microbial cells arrested in their cell cycle has been identified until the present time. In this study we used an antimicrobial peptide derived from α-pheromone, IP-1, targeted against MATa Saccharomyces cerevisiae cells in order to assess its dependence on cell cycle arrest to kill cells. Analysis by flow cytometry and fluorescence microscopy of various null mutations of genes involved in biological processes activated by the pheromone pathway (the mitogen-activated protein kinase pathway, cell cycle arrest, cell proliferation, autophagy, calcium influx) showed that IP-1 requires arrest in G0/G1 in order to kill yeast cells. Isolating cells in different cell cycle phases by elutriation provided further evidence that entry into cell cycle arrest, and not into G1 phase, is necessary if our peptide is to kill yeast cells. We also describe a variant of IP-1 that does not activate the pheromone pathway and consequently does not kill yeast cells that express the pheromone’s receptor; the use of this variant peptide in combination with different cell cycle inhibitors that induce cell cycle arrest independently of the pheromone pathway confirmed that it is cell cycle arrest that is required for the cell death induced by this peptide in yeast. We show that the cell death induced by IP-1 differs from that induced by α-pheromone and depends on FIG1 in a way independent of the cell cycle arrest induced by the pheromone. Thus, IP-1 is the first molecule described that specifically kills microbial cells during cell cycle arrest, a subject of interest beyond the process of mating in yeast cells. The experimental system described in this study should be useful in the study of the mechanisms at play in the communication between cell cycle arrest and cell death on other organisms, hence promoting the development of new antibiotics.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

An Antimicrobial Peptide Induces FIG1-Dependent Cell Death During Cell Cycle Arrest in Yeast

et al. 2018

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“…However, they also become important during the response to toxic chemicals, which can produce ROS directly, or else indirectly through metabolism and attempted detoxification in the vacuole. Toxicity of chemicals that produce ROS in the cell may be mitigated through treatment with antioxidants or intensified through damage to the cellular stress networks (Couto et al, 2016;Sekito et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Oxidative Stress Responses and Nutrient Starvation in MCHM Treated Saccharomyces cerevisiae

Ayers¹,

Sherman²,

Gallagher³

2020

G3 Genes|Genomes|Genetics

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In 2014, the coal cleaning chemical 4-methylcyclohexane methanol (MCHM) spilled into the water supply for 300,000 West Virginians. Initial toxicology tests showed relatively mild results, but the underlying effects on cellular biology were underexplored. Treated wildtype yeast cells grew poorly, but there was only a small decrease in cell viability. Cell cycle analysis revealed an absence of cells in S phase within thirty minutes of treatment. Cells accumulated in G1 over a six-hour time course, indicating arrest instead of death. A genetic screen of the haploid knockout collection revealed 329 high confidence genes required for optimal growth in MCHM. These genes encode three major cell processes: mitochondrial gene expression/translation, the vacuolar ATPase, and aromatic amino acid biosynthesis. The transcriptome showed an upregulation of pleiotropic drug response genes and amino acid biosynthetic genes and downregulation in ribosome biosynthesis. Analysis of these datasets pointed to environmental stress response activation upon treatment. Overlap in datasets included the aromatic amino acid genes ARO1, ARO3, and four of the five TRP genes. This implicated nutrient deprivation as the signal for stress response. Excess supplementation of nutrients and amino acids did not improve growth on MCHM, so the source of nutrient deprivation signal is still unclear. Reactive oxygen species and DNA damage were directly detected with MCHM treatment, but timepoints showed these accumulated slower than cells arrested. We propose that wildtype cells arrest from nutrient deprivation and survive, accumulating oxidative damage through the implementation of robust environmental stress responses.

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Identification of the retinoblastoma (Rb) gene and expression in response to environmental stressors in the intertidal copepod Tigriopus japonicus

et al. 2015

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Tributyltin induces cell cycle arrest at G1 phase in the yeast <i>Saccharomyces cerevisiae</i>

Cited by 5 publications

References 25 publications

An Antimicrobial Peptide Induces FIG1-Dependent Cell Death During Cell Cycle Arrest in Yeast

An Antimicrobial Peptide Induces FIG1-Dependent Cell Death During Cell Cycle Arrest in Yeast

Oxidative Stress Responses and Nutrient Starvation in MCHM Treated Saccharomyces cerevisiae

Identification of the retinoblastoma (Rb) gene and expression in response to environmental stressors in the intertidal copepod Tigriopus japonicus

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