Research, Research Articles
Nutrient sensing and cAMP signaling in yeast: G-protein coupled receptor versus transceptor activation of PKA
Griet Van Zeebroeck1,2,†, Liesbeth Demuyser1,2,†, Zhiqiang Zhang1,2, Ines Cottignie1,2 and Johan M. Thevelein1,2
The herein presented work supports a model, in which nutrient transceptors are evolutionary ancestors of GPCRs, employing a more primitive direct signaling mechanism compared to the indirect cAMP second-messenger signaling mechanism used by GPCRs for activation of PKA.
Novobiocin inhibits membrane synthesis and vacuole formation of Enterococcus faecalis protoplasts
Rintaro Tsuchikado1,#, Satoshi Kami1,#, Sawako Takahashi1 and Hiromi Nishida1
In this study Tsuchikado et al. show that DNA replication is crucial for plasma membrane biosynthesis and vacuole formation in Enterococcus faecalis protoplasts. Novobiocin inhibits DNA replication, blocking cell enlargement and vacuole formation. Extended treatment prevents re-enlargement after removal.
Variants of the human RAD52 gene confer defects in ionizing radiation resistance and homologous recombination repair in budding yeast
Alissa D. Clear1,2,3, Glenn M. Manthey1,2, Olivia Lewis4,5, Isabelle Y. Lopez4,6, Rossana Rico4,7, Shannon Owens8,9, M. Cristina Negritto10, Elise W. Wolf10,11, Jason Xu10,12, Nikola Kenjić13, J. Jefferson P. Perry13, Aaron W. Adamson14, Susan L. Neuhausen14, Adam M. Bailis1,2,15
RAD52 is a key protein in DNA repair and suppresses DNA damage in yeast; however, certain variants affecting BRCA2 mutations fail to correct HRR defects. This suggests that HsRAD52 aids multiple DNA repair mechanisms and could be targeted for use in treating BRCA2-deficient cancers.
Systematic analysis of nuclear gene function in respiratory growth and expression of the mitochondrial genome in S. cerevisiae
Maria Stenger1, Duc Tung Le1, Till Klecker1 and Benedikt Westermann1
Using yeast Saccharomyces cerevisiae, the authors identified 254 nuclear genes essential for respiratory growth and 12 required for viability without mtDNA. They also found 176 genes involved in mitochondrial protein synthesis and mtDNA maintenance, offering a comprehensive view of the processes supporting oxidative phosphorylation.
Histone H3E73Q and H4E53A mutations cause recombinogenic DNA damage
Pedro Ortega1, Desiré García-Pichardo1, Marta San Martin-Alonso1, Ana G. Rondón1, Belén Gómez-González1 and Andrés Aguilera1
This study reveals that conserved residues H3E73 and H4E53 in histones H3 and H4 play a crucial role in maintaining genome stability. Mutations at these sites increase recombinogenic DNA damage, likely due to replication-associated issues rather than transcriptional activity, highlighting their importance in DNA damage prevention and repair.
Sulforaphane alters the acidification of the yeast vacuole
Alexander Wilcox1,#, Michael Murphy1,#, Douglass Tucker1,#, David Laprade1, Breton Roussel1, Christopher Chin2, Victoria Hallisey1, Noah Kozub1, Abraham Brass2 and Nicanor Austriaco1
This study identifies vacuolar pH regulation as a key factor in sulforaphane (SFN) sensitivity, showing that SFN-induced cell death in yeast - and potentially in human cancer cells - is linked to its ability to raise vacuolar or lysosomal pH.
Broad-spectrum antifungal activities and mechanism of drimane sesquiterpenoids
Edruce Edouarzin1, Connor Horn2, Anuja Paudyal2, Cunli Zhang1, Jianyu Lu1, Zongbo Tong1, Guri Giaever3, Corey Nislow3, Raja Veerapandian2, Duy H. Hua1 and Govindsamy Vediyappan2
This study identifies (-)-drimenol as a potent broad-spectrum antifungal agent effective against multiple pathogenic fungi, including drug-resistant strains, and reveals its mechanism of action involves disruption of fungal membranes and targeting Crk1-related pathways, with potential for structural optimization to enhance efficacy.
Stable and destabilized GFP reporters to monitor calcineurin activity in Saccharomyces cerevisiae
Jutta Diessl1, Arpita Nandy1, Christina Schug1, Lukas Habernig1 and Sabrina Büttner1,2
This study introduces GFP-based transcriptional reporters driven by a calcineurin-dependent response element, enabling real-time monitoring of calcineurin activity in live yeast cells for studying stress responses, aging, and antifungal drug screening.
The euchromatic histone mark H3K36me3 preserves heterochromatin through sequestration of an acetyltransferase complex in fission yeast
Paula R. Georgescu1, Matías Capella1, Sabine Fischer-Burkart1 and Sigurd Braun1
This study reveals that the loss of heterochromatin silencing in Set2-deficient cells is due to unrestrained Mst2C activity, highlighting the need for spatially restricted chromatin-modifying enzymes to maintain distinct chromatin states.
Snf1 cooperates with the CWI MAPK pathway to mediate the degradation of Med13 following oxidative stress
June 25, 2018
This article explores the response of eukaryotic cells to environmental stress, highlighting the role of the conserved cyclin C-Cdk8 kinase in determining pro-survival or pro-death programs. Specifically, it discusses how oxidative stress triggers the destruction of Med13 by the SCFGrr1 ubiquitin ligase, releasing cyclin C to promote mitochondrial fission and cell death in Saccharomyces cerevisiae. Additionally, it reveals that the AMP kinase Snf1 activates a separate degron in Med13, contributing to the complex regulation of Med13 degradation following H2O2 stress through the coordination of the cell wall integrity and MAPK pathways.
Importance of polyphosphate in the Leishmania life cycle
June 22, 2018
This article explores the importance of polyphosphate (polyP) in Leishmania parasites, emphasizing the role of the polyP polymerase VTC4 and its impact on parasite survival at higher temperatures. Additionally, it discusses the effects of VTC4 knockout in mouse infections, noting a delay in lesion formation and strong pathology in L. major VTC4 knockout, without confirmation through complementation and no alteration in L. guyanensis infections in mice with VTC4 knockdown.
Antagonism between salicylate and the cAMP signal controls yeast cell survival and growth recovery from quiescence
March 26, 2018
This article describes the effects of salicylate, the main metabolite of aspirin, on S. cerevisiae cells. It outlines how salicylate influences glucose transport, sugar phosphate biosynthesis, and apoptosis, particularly in MnSOD-deficient cells. Furthermore, it emphasizes the significant impact of salicylate on the exit from a quiescent state, inhibiting growth recovery and viability in long-term stationary phase cells. The passage also discusses the potential therapeutic implications of understanding the antagonistic relationship between cAMP and salicylate in targeting quiescent cancer cells with stem-like properties.
Spontaneous mutations in CYC8 and MIG1 suppress the short chronological lifespan of budding yeast lacking SNF1/AMPK
February 19, 2018
Chronologically aging yeast cells are prone to adaptive regrowth, whereby mutants with a survival advantage spontaneously appear and re-enter the cell cycle in stationary phase cultures. Here, Magani et al. identified specific downstream SNF1 targets responsible for CLS extension during CR.
Production of poly-β-1,6-N-acetylglucosamine by MatAB is required for hyphal aggregation and hydrophilic surface adhesion by Streptomyces
February 12, 2018
In this article van Dissel et al. describe new insights to allow better control of liquid-culture morphology of streptomycetes, which may be harnessed to improve growth and industrial exploitation of these highly versatile natural product and enzyme producers.
Non-canonical regulation of glutathione and trehalose biosynthesis characterizes non-Saccharomyces wine yeasts with poor performance in active dry yeast production
January 26, 2018
Several yeast species, belonging to Saccharomyces and non-Saccharomyces genera, play fundamental roles during spontaneous must grape fermentation, and recent studies have shown that mixed fermentations, co-inoculated with S. cerevisiae and non-Saccharomyces strains, can improve wine organoleptic properties. Here, Gamero-Sandemetrio et al. present findings that non-canonical regulation of glutathione and trehalose biosynthesis could cause poor fermentative performance after active dry yeast (ADY) production, as it corroborates the corrective effect of antioxidant treatments, during biomass propagation, with both pure chemicals and food-grade argan oil.
Molecular signature of the imprintosome complex at the mating-type locus in fission yeast
January 16, 2018
Genetic and molecular studies have indicated that an epigenetic imprint at mat1, the sexual locus of fission yeast, initiates mating type switching. Here, Raimondi et al. characterized the recruitment of early players of mating type switching at the mat1 region and suggest a nucleoprotein protective structure defined as imprintosome.
A novel system to monitor mitochondrial translation in yeast
January 13, 2018
In this study Suhm et al. present a novel system to monitor mitochondrial translation by detection of mitochondrial GFP-translation through fluorescence microscopy and flow cytometry in functional mitochondria. This novel tool allows the investigation of the function and regulation of mitochondrial translation during stress signaling, aging and mitochondrial biogenesis.