Research, Research Articles

Cox1 mutation abrogates need for Cox23 in cytochrome c oxidase biogenesis

Richard Dela Cruz1,2, Mi-Young Jeong1 and Dennis R. Winge1

Cox23 is a known conserved assembly factor for cytochrome c oxidase, although its role in cytochrome c oxidase (CcO) biogenesis remains unresolved. To gain additional insights into its role, we isolated spontaneous suppressors of the respiratory growth defect in cox23∆ yeast cells. In this report, we describe the isolation of a robust suppressor of the respiratory defect in cox23∆ cells that mapped to the mitochondrial-encoded Cox1 subunit.

Increased spontaneous recombination in RNase H2-deficient cells arises from multiple contiguous rNMPs and not from single rNMP residues incorporated by DNA polymerase epsilon

Anastasiya Epshtein1, Catherine J. Potenski2, and Hannah L. Klein1

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.

Construction and evaluation of yeast expression networks by database-guided predictions

Katharina Papsdorf1,#, Siyuan Sima1,#, Gerhard Richter2, Klaus Richter1

DNA-Microarrays are powerful tools to obtain expression data on the genome-wide scale. We set out to define a way to cluster microarray data according to their expressional relationship and to obtain information on the significance of this clustering approach.

Optogenetic monitoring identifies phosphatidylthreonine-regulated calcium homeostasis in Toxoplasma gondii

Arunakar Kuchipudi1, Ruben D. Arroyo-Olarte1, Friederike Hoffmann1, Volker Brinkmann2, Nishith Gupta1, 2

Toxoplasma gondii is an obligate intracellular parasite, which inflicts acute as well as chronic infections in a wide range of warm-blooded vertebrates. Using an optogenetic sensor to monitor subcellular calcium in this model intracellular pathogen we found a novel regulatory function of phosphatidylthreonine in calcium signaling.

Filamentation protects Candida albicans from amphotericin B-induced programmed cell death via a mechanism involving the yeast metacaspase, MCA1

David J. Laprade, Melissa S. Brown#, Morgan L. McCarthy#, James J. Ritch, and Nicanor Austriaco

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.

Formaldehyde fixation is detrimental to actin cables in glucose-depleted S. cerevisiae cells

Pavla Vasicova1,#, Mark Rinnerthaler2, Danusa Haskova1, Lenka Novakova1, Ivana Malcova1, Michael Breitenbach2, Jiri Hasek1

Actin filaments form cortical patches and emanating cables in fermenting cells of Saccharomyces cerevisiae. We assume that stability of actin cables reflects the metabolic status of the cell. Based on comparison of live and formaldehyde-fixed cells, our data suggest that formaldehyde affects respiration before fixation and this uneven signaling results in destabilization of actin cables in glucose-deprived cells.

Insights into dynamin-associated disorders through analysis of equivalent mutations in the yeast dynamin Vps1

Laila Moustaq, Iwona I. Smaczynska-de Rooij, Sarah E. Palmer, Christopher J. Marklew, Kathryn R. Ayscough

The dynamins represent a superfamily of proteins that have been shown to function in a wide range of membrane fusion and fission events. An increasing number of mutations in the human classical dynamins, Dyn-1 and Dyn-2 has been reported, with diseases caused by these changes ranging from Charcot-Marie-Tooth disorder to epileptic encephalopathies. This study aimed to use the dynamin-like protein Vps1 of Saccharomyces cerevisiae as a model to gain insights into the mechanistic defects caused by specific dynamin mutations considered to underlie a number of diseases.

Genomic saturation mutagenesis and polygenic analysis identify novel yeast genes affecting ethyl acetate production, a non-selectable polygenic trait

Tom Den Abt1,2, Ben Souffriau1,2, Maria R. Foulquié-Moreno1,2, Jorge Duitama3, and Johan M. Thevelein1,2

Isolation of mutants in populations of microorganisms has been a valuable tool in experimental genetics for decades. The main disadvantage, however, is the inability of isolating mutants in non-selectable polygenic traits. Our study shows that genomic saturation mutagenesis combined with complex trait polygenic analysis could be used successfully to identify causative alleles underlying many non-selectable, polygenic traits in small collections of haploid strains with multiple induced mutations.

Differentiated cytoplasmic granule formation in quiescent and non-quiescent cells upon chronological aging

Hsin-Yi Lee1,3,†, Kuo-Yu Cheng2,3,†, Jung-Chi Chao3 and Jun-Yi Leu3

Stationary phase cultures represent a complicated cell population comprising at least two different cell types, quiescent (Q) and non-quiescent (NQ) cells. The authors show that the cell fate of NQ cells is largely irreversible even if they are allowed to reenter mitosis. Their results reveal that the formation of different granule structures may represent the early stage of cell type differentiation in yeast stationary phase cultures.

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

October 24, 2014

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

October 1, 2014

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

September 1, 2014

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

August 27, 2014

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

Extracellular calcium triggers unique transcriptional programs and modulates staurosporine-induced cell death in Neurospora crassa

August 9, 2014

The results presented here reveal that in Neurospora crassa, extracellular Ca2+ modulates cell death and the transcriptional alterations induced by staurosporine, and lead to the identification of two novel putative Ca2+-binding proteins, encoded by the NCU08524 and NCU06607 genes.

Multiple metabolic requirements for size homeostasis and initiation of division in Saccharomyces cerevisiae

August 1, 2014

This article reveals an unexpected diversity in the G1 cell cycle phenotypes of metabolic and biosynthetic Saccharomyces cerevisiae mutants, suggesting that growth requirements for cell division are multiple, distinct and imposed throughout the G1 phase of the cell cycle.

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.

Effect of paraquat-induced oxidative stress on gene expression and aging of the filamentous ascomycete Podospora anserina

June 22, 2014

In this article, paraquat is used to experimentally induce strong cellular oxidative stress in Podospora anserina wild-type cultures of different age, finding that this treatment has profound effects on gene expression, growth and lifespan.

Heat shock protein 90 and calcineurin pathway inhibitors enhance the efficacy of triazoles against Scedosporium prolificans via induction of apoptosis

June 2, 2014

This article reports for the first time that posaconazole (PCZ) or itraconazolein (ICZ) in combination with the calcineurin inhibitor tacrolimus or the Hsp90 inhibitor 17-demethoxy-17-(2-propenylamino) geldanamycin renders S. prolificans exquisitely sensitive to PCZ or ICZ via apoptosis.

At neutral pH the chronological lifespan of Hansenula polymorpha increases upon enhancing the carbon source concentrations

May 20, 2014

The data presented in this work indicate that in H. polymorpha at neutral pH the chronological lifespan invariably extends upon increasing the carbon source concentration.

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