scholarly journals Punctuated Aneuploidization of the Budding Yeast Genome

Genetics ◽  
2020 ◽  
Vol 216 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Lydia R. Heasley ◽  
Ruth A. Watson ◽  
Juan Lucas Argueso
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Tumor Cells ◽  
Genomic Instability ◽  
High Frequency ◽  
Budding Yeast ◽  
Cell Types ◽  
Eukaryotic Cell ◽  
Yeast Genome ◽  
Single Chromosome ◽  
Brewing Yeasts

Remarkably complex patterns of aneuploidy have been observed in the genomes of many eukaryotic cell types, ranging from brewing yeasts to tumor cells. Such aberrant karyotypes are generally thought to take shape progressively over many generations, but evidence also suggests that genomes may undergo faster modes of evolution. Here, we used diploid Saccharomyces cerevisiae cells to investigate the dynamics with which aneuploidies arise. We found that cells selected for the loss of a single chromosome often acquired additional unselected aneuploidies concomitantly. The degrees to which these genomes were altered fell along a spectrum, ranging from simple events affecting just a single chromosome, to systemic events involving many. The striking complexity of karyotypes arising from systemic events, combined with the high frequency at which we detected them, demonstrates that cells can rapidly achieve highly altered genomic configurations during temporally restricted episodes of genomic instability.

scholarly journals Punctuated Aneuploidization of the Budding Yeast Genome

2020 ◽  
Author(s):  
Lydia R. Heasley ◽  
Ruth A. Watson ◽  
Juan Lucas Argueso
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Tumor Cells ◽  
Genomic Instability ◽  
High Frequency ◽  
Budding Yeast ◽  
Cell Types ◽  
Eukaryotic Cell ◽  
Yeast Genome ◽  
Single Chromosome ◽  
Brewing Yeasts

AbstractRemarkably complex patterns of aneuploidy have been observed in the genomes of many eukaryotic cell types, ranging from brewing yeasts to tumor cells (1, 2). Such aberrant karyotypes are generally thought to take shape progressively over many generations, but evidence also suggests that genomes may undergo faster modes of evolution (2, 3). Here, we used diploid Saccharomyces cerevisiae cells to investigate the dynamics with which aneuploidies arise. We found that cells selected for the loss of a single chromosome often acquired additional unselected aneuploidies concomitantly. The degrees to which these genomes were altered fell along a spectrum, ranging from simple events affecting just a single chromosome, to systemic events involving many. The striking complexity of karyotypes arising from systemic events, combined with the high frequency at which we detected them, demonstrates that cells can rapidly achieve highly altered genomic configurations during temporally restricted episodes of genomic instability.

G1 cyclins regulate proliferation of the budding yeast Saccharomyces cerevisiae

1992 ◽  
Vol 70 (10-11) ◽  
pp. 946-953
Author(s):  
Adele Rowley ◽  
Gerald C. Johnston ◽  
Richard A. Singer
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Protein Kinase ◽  
Budding Yeast ◽  
Cell Types ◽  
Eukaryotic Cell ◽  
Yeast Saccharomyces Cerevisiae ◽  
Functional Conservation ◽  
Cycle Regulation

The eukaryotic cell cycle is regulated at two points, the G1-S and G2-M boundaries. The molecular basis for these regulatory activities has recently been elucidated, in large part by the use of molecular and genetic analyses using unicellular yeast. The molecular characterization of cell-cycle regulation has revealed striking functional conservation among evolutionarily diverse cell types. For many eukaryotic cells, regulation of cell proliferation occurs primarily in the G1 interval. The G2 regulatory step, termed start, requires the activation of a highly conserved p34 protein kinase by association with a functionally redundant family of proteins, the G1 cyclins. Here we review studies using the genetically tractable budding yeast Saccharomyces cerevisiae, which have provided insight into the role of G1 cyclins in the regulation of start.Key words: cell cycle, cyclin proteins, cdc2 protein kinase, start.

scholarly journals FREQUENCY AND DIRECTIONALITY OF GENE CONVERSION EVENTS INVOLVING THE CYC7-H3 MUTATION IN SACCHAROMYCES CEREVISIAE

Genetics ◽  
1986 ◽  
Vol 114 (2) ◽  
pp. 347-361
Author(s):  
Patricia J Pukkila ◽  
Michael D Stephens ◽  
David M Binninger ◽  
Beverly Errede
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Gene Conversion ◽  
High Frequency ◽  
Yeast Genome ◽  
Junction Region ◽  
Sequence Comparisons ◽  
Site Specific ◽  
Site Specific Recombination ◽  
Conversion Frequency ◽  
Aberrant Segregation

ABSTRACT The CYC7-H3 mutation is a 5-kb deletion that causes overproduction of iso-2 cytochrome c. Unlike most mutations in yeast, the CYC7-H3 mutation is preferentially lost when it is involved in a gene conversion event. We have shown that cloned copies of CYC7-H3 DNA that are inserted into the yeast genome are associated with a high frequency of recombination and aberrant segregation events. Since parity in conversion frequency was observed when the extensive insertion/deletion heterozygosity at this locus was eliminated, we conclude that the CYC7-H3 sequences are inherently capable of acting as donors or recipients in gene conversion events, although they are unlikely to act as donors when they are located opposite a large heterology. DNA sequence comparisons revealed similarities between the CYC7-H3 junction region and the 2-µm circle DNA region that is involved in site-specific recombination.

scholarly journals Developing a Yeast Platform Strain for an Enhanced Taxadiene Biosynthesis by CRISPR/Cas9

Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 147
Author(s):  
Joseph C. Utomo ◽  
Fabio C. Chaves ◽  
Philippe Bauchart ◽  
Vincent J. J. Martin ◽  
Dae-Kyun Ro
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Anticancer Drug ◽  
Biosynthetic Pathway ◽  
Budding Yeast ◽  
Yeast Genome ◽  
Yeast Saccharomyces Cerevisiae ◽  
Geranylgeranyl Pyrophosphate ◽  
Common Precursor ◽  
The Future ◽  
Terpenoid Pathway

Paclitaxel is an important diterpenoid commonly used as an anticancer drug. Although the paclitaxel biosynthetic pathway has been mostly revealed, some steps remain to be elucidated. The difficulties in plant transformations and the scarcity of the precursor of paclitaxel, (+)-taxa-4(5), 11(12)-diene (taxadiene), have hindered the full comprehension of paclitaxel biochemistry and, therefore, its production by biotechnological approaches. One solution is to use the budding yeast, Saccharomyces cerevisiae, as a platform to elucidate the paclitaxel biosynthesis. As taxadiene is a diterpenoid, its common precursor, geranylgeranyl pyrophosphate (GGPP), needs to be increased in yeast. In this study, we screened various GGPP synthases (GGPPS) to find the most suitable GGPPS for taxadiene production in yeast. We also optimized the taxadiene production by increasing the flux toward the terpenoid pathway. Finally, to remove selection markers, we integrated the required genes using a CRISPR/Cas9 system in the yeast genome. Our result showed that a titer of 2.02 ± 0.40 mg/L (plasmid) and 0.41 ± 0.06 mg/L (integrated) can be achieved using these strategies. This platform strain can be used to readily test the gene candidates for microbial paclitaxel biosynthesis in the future.

scholarly journals Plasma membrane damage limits replicative lifespan in yeast and human fibroblasts

2021 ◽  
Author(s):  
Keiko Kono ◽  
Yoshikazu Johmura ◽  
Yohsuke Moriyama ◽  
Yumiko Masukagami ◽  
Koutarou Nishimura ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cellular Senescence ◽  
Human Fibroblasts ◽  
Membrane Damage ◽  
Cell Types ◽  
Eukaryotic Cell ◽  
Yeast Genome ◽  
Replicative Lifespan ◽  
Aaa Atpase ◽  
Plasma Membrane Damage

AbstractPlasma membrane damage (PMD) occurs in all cell types due to environmental perturbation and cell-autonomous activities. However, cellular outcomes of PMD remain largely unknown except for recovery or death. Here, using yeast and human fibroblasts, we show that cellular senescence, irreversible cell cycle arrest contributing to organismal aging, is the third outcome of PMD. To identify the genes essential for PMD response, we performed a systematic yeast genome-wide screen. The screen identified 48 genes. The top hits in the screen are the endosomal sorting complexes required for transport (ESCRT) genes. Strikingly, the replicative lifespan regulator genes are enriched in our 48 hits, and indeed, PMD limits the replicative lifespan in budding yeast; the ESCRT activator AAA-ATPase VPS4-overexpression extends it. In normal human fibroblasts, PMD induces cellular senescence via p53. Our study demonstrates that PMD limits replicative lifespan in two different eukaryotic cell types and highlights an underappreciated but ubiquitous senescent cell subtype, namely PMD-dependent senescent cells.

scholarly journals Filamentous growth of the budding yeast Saccharomyces cerevisiae induced by overexpression of the WHI2 gene

Microbiology ◽  
1997 ◽  
Vol 143 (6) ◽  
pp. 1867-1876 ◽  
Author(s):  
P. A. Radcliffe ◽  
K. M. Binley ◽  
J. Trevethick ◽  
M. Hall ◽  
P. E. Sudbery
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Budding Yeast ◽  
Filamentous Growth ◽  
Yeast Saccharomyces Cerevisiae

scholarly journals A high-resolution protein architecture of the budding yeast genome

Nature ◽  
2021 ◽  
Author(s):  
Matthew J. Rossi ◽  
Prashant K. Kuntala ◽  
William K. M. Lai ◽  
Naomi Yamada ◽  
Nitika Badjatia ◽  
...  
Keyword(s):  
High Resolution ◽  
Budding Yeast ◽  
Yeast Genome ◽  
Protein Architecture

scholarly journals The Blockade of Tumoral IL1β-Mediated Signaling in Normal Colonic Fibroblasts Sensitizes Tumor Cells to Chemotherapy and Prevents Inflammatory CAF Activation

2021 ◽  
Vol 22 (9) ◽  
pp. 4960
Author(s):  
Natalia Guillén Díaz-Maroto ◽  
Gemma Garcia-Vicién ◽  
Giovanna Polcaro ◽  
María Bañuls ◽  
Nerea Albert ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Cell Types ◽  
Colorectal Tumor ◽  
Cytotoxic Drugs ◽  
Differential Sensitivity ◽  
Paracrine Signaling ◽  
Inflammatory Phenotype ◽  
Heterotypic Interactions ◽  
Carcinoma Associated Fibroblasts

Heterotypic interactions between newly transformed cells and normal surrounding cells define tumor’s fate in incipient carcinomas. Once homeostasis has been lost, normal resident fibroblasts become carcinoma-associated fibroblasts, conferring protumorogenic properties on these normal cells. Here we describe the IL1β-mediated interplay between cancer cells and normal colonic myofibroblasts (NCFs), which bestows differential sensitivity to cytotoxic drugs on tumor cells. We used NCFs, their conditioned media (CM), and cocultures with tumor cells to characterize the IL1β-mediated crosstalk between both cell types. We silenced IL1β in tumor cells to demonstrate that such cells do not exert an influence on NCFs inflammatory phenotype. Our results shows that IL1β is overexpressed in cocultured tumor cells. IL1β enables paracrine signaling in myofibroblasts, converting them into inflammatory-CAFs (iCAF). IL1β-stimulated-NCF-CM induces migration and differential sensitivity to oxaliplatin in colorectal tumor cells. Such chemoprotective effect has not been evidenced for TGFβ1-driven NCFs. IL1β induces the loss of a myofibroblastic phenotype in NCFs and acquisition of iCAF traits. In conclusion, IL1β-secreted by cancer cells modify surrounding normal fibroblasts to confer protumorogenic features on them, particularly tolerance to cytotoxic drugs. The use of IL1β-blocking agents might help to avoid the iCAF traits acquisition and consequently to counteract the protumorogenic actions these cells.

scholarly journals High-frequency burst spiking in layer 5 thick-tufted pyramids of rat primary somatosensory cortex encodes exploratory touch

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Christiaan P. J. de Kock ◽  
Jean Pie ◽  
Anton W. Pieneman ◽  
Rebecca A. Mease ◽  
Arco Bast ◽  
...  
Keyword(s):  
Somatosensory Cortex ◽  
Information Content ◽  
High Frequency ◽  
Temporal Structure ◽  
Cell Types ◽  
Primary Somatosensory Cortex ◽  
Excitatory Cell ◽  
Cortical Microcircuit ◽  
Subcortical Regions ◽  
Frequency Burst

AbstractDiversity of cell-types that collectively shape the cortical microcircuit ensures the necessary computational richness to orchestrate a wide variety of behaviors. The information content embedded in spiking activity of identified cell-types remain unclear to a large extent. Here, we recorded spike responses upon whisker touch of anatomically identified excitatory cell-types in primary somatosensory cortex in naive, untrained rats. We find major differences across layers and cell-types. The temporal structure of spontaneous spiking contains high-frequency bursts (≥100 Hz) in all morphological cell-types but a significant increase upon whisker touch is restricted to layer L5 thick-tufted pyramids (L5tts) and thus provides a distinct neurophysiological signature. We find that whisker touch can also be decoded from L5tt bursting, but not from other cell-types. We observed high-frequency bursts in L5tts projecting to different subcortical regions, including thalamus, midbrain and brainstem. We conclude that bursts in L5tts allow accurate coding and decoding of exploratory whisker touch.

A Novel Ty1-Mediated Fragmentation Method for Native and Artificial Yeast Chromosomes Reveals That the Mouse Steel Gene is a Hotspot for Ty1 Integration

Genetics ◽  
1996 ◽  
Vol 143 (2) ◽  
pp. 673-683
Author(s):  
Jacob Z Dalgaard ◽  
Mukti Banerjee ◽  
M Joan Curcio
Keyword(s):  
Transcription Unit ◽  
Yeast Genome ◽  
Physical Analysis ◽  
Single Chromosome ◽  
Artificial Chromosomes ◽  
Unique Site ◽  
High Fraction ◽  
A Site ◽  
Yeast Artificial Chromosomes ◽  
Random Insertion

Abstract We have developed a powerful new tool for the physical analysis of genomes called Ty1-mediated chromosomal fragmentation and have used the method to map 24 retrotransposon insertions into two different mousederived yeast artificial chromosomes (YACs). Expression of a plasmid-encoded GAL1:Ty1 fusion element marked with the retrotransposition indicator gene, ade2AI, resulted in a high fraction of cells that sustained a single Ty1 insertion marked with ADE2. Strains in which Ty1ADE2 inserted into aYAC were identified by cosegregation of the ADE2 gene with the URA3-marked YAC. Ty1ADE2 elements also carried a site for the endonuclease I-DmoI, which we demonstrate is not present anywhere in the yeast genome. Consequently, I-DmoI cleaved a single chromosome or YAC at the unique site of Ty1ADE2 insertion, allowing rapid mapping of integration events. Our analyses showed that the frequency of Ty1ADE2 integration into YACs is equivalent to or higher than that expected based on random insertion. Remarkably, the 50-kb transcription unit of the mouse Steel locus was shown to be a highly significant hotspot for Ty1 integration. The accessibility of mammalian transcription units to Ty1 insertion stands in contrast to that of yeast transcription units.

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