Research, Research Reports

Loss of wobble uridine modification in tRNA anticodons interferes with TOR pathway signaling

Viktor Scheidt1,#, André Jüdes1,#, Christian Bär1,2,#, Roland Klassen1 and Raffael Schaffrath1

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.

Measurement of apoptosis by SCAN©, a system for counting and analysis of fluorescently labelled nuclei

Neta Shlezinger1,#, Elad Eizner1,2,#, Stas Dubinchik2, Anna Minz-Dub1, Rachel Tetroashvili1, Adi Reider1, Amir Sharon1

This work reports on a system for analyses of apoptosis-like programmed cell death in fungal hyphae that is composed of several modules, which enable automatic quantification of nuclei with chromatin condensation and DNA strand break in large datasets according to nuclei-associated fluorescent markers.

Rewiring yeast acetate metabolism through MPC1 loss of function leads to mitochondrial damage and decreases chronological lifespan

Ivan Orlandi1,2, Damiano Pellegrino Coppola2 and Marina Vai1,2

This work shows that MPC1-deficient cells make up for their impairment in mitochondrial pyruvate with a metabolic rewiring which involves several intermediates of the mitochondrially localized TCA cycle and the cytosolic glyoxylate shunt but ultimately results in a pro-aging process.

Overexpression of the transcription factor Yap1 modifies intracellular redox conditions and enhances recombinant protein secretion

Marizela Delic1,2, Alexandra B. Graf2,3, Gunda Koellensperger1,4, Christina Haberhauer-Troyer1,4, Stephan Hann1,4, Diethard Mattanovich1,2, Brigitte Gasser1,2

This article investigates the role of Yap1 during the production of recombinant secretory proteins in glucose based growth conditions in Pichia pastoris, and reports a novel role of Yap1 during ER-resident oxidative protein folding.

Functional analysis of lipid metabolism genes in wine yeasts during alcoholic fermentation at low temperature

María López-Malo1,2, Estéfani García-Ríos1, Rosana Chiva1 and José Manuel Guillamon1

This study confirms the importance of specific genes in growth and fermentation activity of Saccharomyces cerevisiae at low temperature.

Angiotensin II type 1 receptor blockers increase tolerance of cells to copper and cisplatin

Pieter Spincemaille1,+, Gursimran Chandhok2,+, Andree Zibert2, Hartmut Schmidt2, Jef Verbeek3, Patrick Chaltin4,5, Bruno P.A. Cammue1,6,#, David Cassiman3, Karin Thevissen1,#

This study reports the identification of the drug class of Angiotensin II Type 1 receptor blockers (ARBs) and shows that specific ARBs increase yeast tolerance to Cu and Cp, and affect markers of Cu-induced apoptosis. Likewise, this study finds that specific ARBs increase human cell line tolerance to Cu and decrease the prevalence of apoptotic markers.

An extensive endoplasmic reticulum-localised glycoprotein family in trypanosomatids

Harriet Allison1, Amanda J. O’Reilly1, Jeremy Sternberg2 and Mark C. Field1

This work describes a novel family of type I membrane proteins ("invariant glycoproteins") and proposes them as trypanosomatid-specific ER-localised glycoproteins, with potential contributions to life cycle progression and immunity, that utilise oligomerisation as an ER retention mechanism.

Time resolved DNA occupancy dynamics during the respiratory oscillation uncover a global reset point in the yeast growth program

Cornelia Amariei, Rainer Machné, Viktor Stolc, Tomoyoshi Soga, Masaru Tomita and Douglas B. Murray

Using multiple approaches, this work implies a nucleosome focusing event as a key step that resets transcription during the respiratory oscillation.

Cell wall dynamics modulate acetic acid-induced apoptotic cell death of Saccharomyces cerevisiae

António Rego#, Ana Marta Duarte#, Flávio Azevedo#, Maria João Sousa, Manuela Côrte-Real and Susana R. Chaves

This work characterizes the involvement of MAPK signaling pathways in cell death induced by acetic acid in Saccharomyces cerevisiae.

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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.

Micafungin induced apoptosis in Candida parapsilosis independent of its susceptibility to micafungin

October 23, 2015

Shirazi et al. studied the effects of the cell wall inhibitor micafungin (MICA) on apoptosis in both MICA-susceptible (MICA-S) and MICA–non-susceptible (MICA-NS) Candida parapsilosis.

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.