Research, Research Reports
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.
Increased spontaneous recombination in RNase H2-deficient cells arises from multiple contiguous rNMPs and not from single rNMP residues incorporated by DNA polymerase epsilon
May 15, 2016
Ribonucleotides (rNMPs) can become embedded in DNA from insertion by DNA polymerases, failure to remove Okazaki fragment primers, R-loops that can prime replication, and RNA/cDNA-mediated recombination. We report here that recombination is not stimulated by rNMPs incorporated by the replicative polymerase epsilon. Instead, recombination seems to be stimulated by multiple contiguous rNMPs, which may arise from R-loops or replication priming events.
Filamentation protects Candida albicans from amphotericin B-induced programmed cell death via a mechanism involving the yeast metacaspase, MCA1
April 25, 2016
Candida albicans proliferates in two distinct cell types: blastopores and filaments. Programmed cell death is a controlled form of cell suicide that occurs when C. albicans cells are exposed to fungicidal drugs like amphotericin B and caspofungin, and to other stressful conditions. We provide evidence that programmed cell death is cell-type specific in yeast: Filamentous C. albicans cells are more resistant to amphotericin B- and caspofungin-induced programmed cell death than their blastospore counterparts. Our genetic data suggest that this phenomenon is mediated by a protective mechanism involving the yeast metacaspase, MCA1.
Towards understanding the gliotoxin detoxification mechanism: in vivo thiomethylation protects yeast from gliotoxin cytotoxicity
February 19, 2016
Gliotoxin is a mycotoxin produced by some species of ascomycete fungi including the opportunistic human pathogen Aspergillus fumigatus. In order to produce gliotoxin the host organism needs to have evolved a self-protection mechanism. The authors demonstrate that the activity of a novel thiomethyltransferase is requiered for protection against exogenous gliotoxin and provide implications for understanding the evolution of gliotoxin self-protection mechanisms.
The transcriptional repressor Sum1p counteracts Sir2p in regulation of the actin cytoskeleton, mitochondrial quality control and replicative lifespan in Saccharomyces cerevisiae
January 18, 2016
Increasing the stability or dynamics of the actin cytoskeleton can extend lifespan in C. elegans and S. cerevisiae. Actin cables of budding yeast, bundles of actin filaments that mediate cargo transport, affect lifespan control through effects on mitochondrial quality control. Here, we report that Sum1p and Sir2p inversely regulate actin and mitochondrial maintenance, as well as lifespan.
Human Thyroid Cancer-1 (TC-1) is a vertebrate specific oncogenic protein that protects against copper and pro-apoptotic genes in yeast
June 25, 2015
The human Thyroid Cancer-1 (hTC-1) protein, also known as C8orf4 was initially identified as a gene that was up-regulated in human thyroid cancer. This article reports that hTC-1 is a peptide that prevents the effects of over-expressing Bax in yeast. In sum, the results indicate that hTC-1 is a pro-survival protein that retains its function when heterologously expressed in yeast. Thus yeast is a useful model to characterize the potential roles in cell death and survival of cancer related genes.
Exogenous folates stimulate growth and budding of Candida glabrata
May 1, 2015
Folate, vitamin B9, is well recognized as being essential for cell growth. The utilization of folate is common to all cells, but the source of it may be quite different. This article reports a novel response of yeast to folates that may increase the utility of yeast as a model to study folate transport and signaling.
Loss of wobble uridine modification in tRNA anticodons interferes with TOR pathway signaling
November 29, 2014
The herein presented data suggest that proper TOR signaling requires intact tRNA modifications and that loss of U34 modifications impinges on the TOR-sensitive NCR branch via Gln3 misregulation.
Exogenous addition of histidine reduces copper availability in the yeast Saccharomyces cerevisiae
July 6, 2014
The herein presented results indicate that in Saccharomyces cerevisiae, histidine cytotoxicity is associated with low copper availability inside cells, not with impaired copper uptake. Furthermore, it suggests that histidine cytotoxicity is involved in deficiency of mitochondrial copper.
Deletion of AIF1 but not of YCA1/MCA1 protects Saccharomyces cerevisiae and Candida albicans cells from caspofungin-induced programmed cell death
January 15, 2014
This work suggests that deleting AIF1 but not YCA1/MCA1 protects S. cerevisiae and Candida albicans from caspofungin-induced cell death. This is not only the first time that AIF1 has been specifically tied to cell death in Candida but also the first time that caspofungin resistance has been linked to the cell death machinery in yeast.