Vol. 02, 2015

Groupthink: chromosomal clustering during transcriptional memory

Kevin A. Morano

In this article, the authors comment on the study "NO1 transcriptional memory leads to DNA zip code-dependent interchromosomal clustering." by Brickner et al. (Microbial Cell, 2015), discussing the importance and molecular mechanisms of chromosomal clustering during transcriptional memory.

Yeast proteinopathy models: a robust tool for deciphering the basis of neurodegeneration

Amit Shrestha1, 2 and Lynn A. Megeney1, 2, 3

Protein quality control or proteostasis is an essential determinant of basic cell health and aging. Eukaryotic cells have evolved a number of proteostatic mechanisms to ensure that proteins retain functional conformation, or are rapidly degraded when proteins misfold or self-aggregate. This article discusses the use of budding yeast as a robust proxy to study the intersection between proteostasis and neurodegenerative disease.

INO1 transcriptional memory leads to DNA zip code-dependent interchromosomal clustering

Donna Garvey Brickner, Robert Coukos and Jason H. Brickner

Many genes localize at the nuclear periphery through physical interaction with the nuclear pore complex (NPC). We have found that the yeast INO1 gene is targeted to the NPC both upon activation and for several generations after repression, a phenomenon called epigenetic transcriptional memory. Targeting of INO1 to the NPC requires distinct cis-acting promoter DNA zip codes under activating conditions and under memory conditions. When at the nuclear periphery, active INO1 clusters with itself and with other genes that share the GRS I zip code. Here, we show that during memory, the two alleles of INO1 cluster in diploids and endogenous INO1 clusters with an ectopic INO1 in haploids. After repression, INO1 does not cluster with GRS I - containing genes. Furthermore, clustering during memory requires Nup100 and two sets of DNA zip codes...

A central role for TOR signalling in a yeast model for juvenile CLN3 disease

Michael E. Bond1, Rachel Brown1, Charalampos Rallis3,4, Jürg Bähler3,4 and Sara E. Mole1,2,3

Yeasts provide an excellent genetically tractable eukaryotic system for investigating the function of genes in their biological context, and are especially relevant for those conserved genes that cause disease. Bond et al. study the role of btn1, the orthologue of a human gene that underlies an early onset neurodegenerative disease (juvenile CLN3 disease, neuronal ceroid lipofuscinosis (NCLs) or Batten disease) in the fission yeast Schizosaccharomyces pombe.

Histone deacetylases: revealing the molecular base of dimorphism in pathogenic fungi

Alberto Elías-Villalobos1,2, Dominique Helmlinger2 and José I. Ibeas1

Fungi, as every living organism, interact with the external world and have to adapt to its fluctuations. For pathogenic fungi, such interaction involves adapting to the hostile environment of their host. Survival depends on the capacity of fungi to detect and respond to external stimuli, which is achieved through a tight and efficient genetic control. Elías-Villalobos et al. propose that histone acetylation is critical to the proper timing and induction of transcription of the genes encoding factors that coordinate changes in morphology with pathogenesis.

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

Fazal Shirazi1, Russel E. Lewis1,2, Dimitrios P. Kontoyiannis1

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.

Oxygen availability strongly affects chronological lifespan and thermotolerance in batch cultures of Saccharomyces cerevisiae

Markus M.M. Bisschops1,3,#, Tim Vos1,#, Rubén Martínez-Moreno2,4, Pilar de la Torre Cortés1, Jack T. Pronk1, Pascale Daran-Lapujade1

Stationary-phase (SP) batch cultures of Saccharomyces cerevisiae, in which growth has been arrested by carbon-source depletion, are widely applied to study chronological lifespan, quiescence and SP-associated robustness. Based on this type of experiments, typically performed under aerobic conditions, several roles of oxygen in aging have been proposed. However, SP in anaerobic yeast cultures has not been investigated in detail. Here, we use the unique capability of S. cerevisiae to grow in the complete absence of oxygen to directly compare SP in aerobic and anaerobic bioreactor cultures. This comparison revealed strong positive effects of oxygen availability on adenylate energy charge, longevity and thermotolerance during SP. A low thermotolerance of...

Electron microscopy for ultrastructural analysis and protein localization in Saccharomyces cerevisiae

Andri Frankl, Muriel Mari and Fulvio Reggiori

The yeast Saccharomyces cerevisiae is a key model system for studying of a multitude of cellular processes because of its amenability to genetics, molecular biology and biochemical procedures. The goal of this review is to guide researchers that want to investigate a particular process at the ultrastructural level in yeast by aiding in the selection of the most appropriate approach to visualize a specific structure or subcellular compartment.

Starting with a degron: N-terminal formyl-methionine of nascent bacterial proteins contributes to their proteolytic control

R. Jürgen Dohmen

In this article, the author comments on the study "Formyl-methionine as a degradation signal at the N-termini of bacterial proteins." by Piatkov et al. (Microbial Cell, 2015), discussing a novel N-terminal degradation signal (N-degron) that targets nascent proteins for degradation in Escherichia coli by a new branch of the bacterial N-end rule pathway, termed the fMet/N-end rule pathway

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Groupthink: chromosomal clustering during transcriptional memory

Kevin A. Morano

In this article, the authors comment on the study "NO1 transcriptional memory leads to DNA zip code-dependent interchromosomal clustering." by Brickner et al. (Microbial Cell, 2015), discussing the importance and molecular mechanisms of chromosomal clustering during transcriptional memory.

Yeast proteinopathy models: a robust tool for deciphering the basis of neurodegeneration

Amit Shrestha1, 2 and Lynn A. Megeney1, 2, 3

Protein quality control or proteostasis is an essential determinant of basic cell health and aging. Eukaryotic cells have evolved a number of proteostatic mechanisms to ensure that proteins retain functional conformation, or are rapidly degraded when proteins misfold or self-aggregate. This article discusses the use of budding yeast as a robust proxy to study the intersection between proteostasis and neurodegenerative disease.

INO1 transcriptional memory leads to DNA zip code-dependent interchromosomal clustering

Donna Garvey Brickner, Robert Coukos and Jason H. Brickner

Many genes localize at the nuclear periphery through physical interaction with the nuclear pore complex (NPC). We have found that the yeast INO1 gene is targeted to the NPC both upon activation and for several generations after repression, a phenomenon called epigenetic transcriptional memory. Targeting of INO1 to the NPC requires distinct cis-acting promoter DNA zip codes under activating conditions and under memory conditions. When at the nuclear periphery, active INO1 clusters with itself and with other genes that share the GRS I zip code. Here, we show that during memory, the two alleles of INO1 cluster in diploids and endogenous INO1 clusters with an ectopic INO1 in haploids. After repression, INO1 does not cluster with GRS I - containing genes. Furthermore, clustering during memory requires Nup100 and two sets of DNA zip codes...

A central role for TOR signalling in a yeast model for juvenile CLN3 disease

Michael E. Bond1, Rachel Brown1, Charalampos Rallis3,4, Jürg Bähler3,4 and Sara E. Mole1,2,3

Yeasts provide an excellent genetically tractable eukaryotic system for investigating the function of genes in their biological context, and are especially relevant for those conserved genes that cause disease. Bond et al. study the role of btn1, the orthologue of a human gene that underlies an early onset neurodegenerative disease (juvenile CLN3 disease, neuronal ceroid lipofuscinosis (NCLs) or Batten disease) in the fission yeast Schizosaccharomyces pombe.

Histone deacetylases: revealing the molecular base of dimorphism in pathogenic fungi

Alberto Elías-Villalobos1,2, Dominique Helmlinger2 and José I. Ibeas1

Fungi, as every living organism, interact with the external world and have to adapt to its fluctuations. For pathogenic fungi, such interaction involves adapting to the hostile environment of their host. Survival depends on the capacity of fungi to detect and respond to external stimuli, which is achieved through a tight and efficient genetic control. Elías-Villalobos et al. propose that histone acetylation is critical to the proper timing and induction of transcription of the genes encoding factors that coordinate changes in morphology with pathogenesis.

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

Fazal Shirazi1, Russel E. Lewis1,2, Dimitrios P. Kontoyiannis1

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.

Next

Histone deacetylases: revealing the molecular base of dimorphism in pathogenic fungi

Alberto Elías-Villalobos1,2, Dominique Helmlinger2 and José I. Ibeas1

Fungi, as every living organism, interact with the external world and have to adapt to its fluctuations. For pathogenic fungi, such interaction involves adapting to the hostile environment of their host. Survival depends on the capacity of fungi to detect and respond to external stimuli, which is achieved through a tight and efficient genetic control. Elías-Villalobos et al. propose that histone acetylation is critical to the proper timing and induction of transcription of the genes encoding factors that coordinate changes in morphology with pathogenesis.

Electron microscopy for ultrastructural analysis and protein localization in Saccharomyces cerevisiae

Andri Frankl, Muriel Mari and Fulvio Reggiori

The yeast Saccharomyces cerevisiae is a key model system for studying of a multitude of cellular processes because of its amenability to genetics, molecular biology and biochemical procedures. The goal of this review is to guide researchers that want to investigate a particular process at the ultrastructural level in yeast by aiding in the selection of the most appropriate approach to visualize a specific structure or subcellular compartment.

A bacterial volatile signal for biofilm formation

Yun Chen2, Kevin Gozzi1, and Yunrong Chai1

Bacteria constantly monitor the environment they reside in and respond to potential changes in the environment through a variety of signal sensing and transduction mechanisms in a timely fashion. In their recent study (Chen, et al. mBio (2015), 6: e00392-15), the authors demonstrated that the soil bacterium Bacillus subtilis uses acetic acid as a volatile signal to coordinate the timing of biofilm formation within physically separated cells in the community. They also showed that the bacterium possesses an intertwined gene network to produce, secrete, sense, and respond to acetic acid, in stimulating biofilm formation.

The great escape: Pseudomonas breaks out of the lung

Angelica Zhang1, Stephanie M. Rangel1, and Alan R. Hauser1,2

The Gram-negative bacterium Pseudomonas aeruginosa is a major cause of hospital-acquired infections and the focus of much attention due to its resistance to many conventional antibiotics. This article discusses the potential mechanisms by which these processes occur as well as the novel techniques used to study ExoS function in vivo.

Peering into the ‘black box’ of pathogen recognition by cellular autophagy systems

Shu-chin Lai# and Rodney J Devenish

Autophagy is an intracellular process that plays an important role in protecting eukaryotic cells and maintaining intracellular homeostasis. This review summarises the available evidence regarding the specific recognition of invading pathogens by which they are targeted into host autophagy pathways.

Per aspera ad astra: When harmful chromosomal translocations become a plus value in genetic evolution. Lessons from Saccharomyces cerevisiae

Valentina Tosato and Carlo V. Bruschi

This review will focus on chromosomal translocations (either spontaneous or induced) in budding yeast. Indeed, very few organisms tolerate so well aneuploidy like Saccharomyces, allowing in depth studies on chromosomal numerical aberrations. The phenomenon of post-translocational adaptation (PTA) is discussed, providing some new unpublished data and proposing the hypothesis that translocations may drive evolution through adaptive genetic selection.

Intracellular phase for an extracellular bacterial pathogen: MgtC shows the way

Audrey Bernut1,#, Claudine Belon1, Chantal Soscia2, Sophie Bleves2, Anne-Béatrice Blanc-Potard1

This article discusses the article "A macrophage subversion factor is shared by intracellular and extracellular pathogens" by Belon et al. (PLoS Pathogens 11(6): e1004969, 2015).

The role of transcriptional ‘futile cycles’ in autophagy and microbial pathogenesis

Guowu Hu1, Travis McQuiston1, Amélie Bernard2, Yoon-Dong Park1, Jin Qiu1, Ali Vural3, Nannan Zhang1, Scott R. Waterman1, Nathan H. Blewett4, Timothy G. Myers5, John H. Kehrl3, Gulbu Uzel1, Daniel J. Klionsky2 and Peter R. Williamson1

Eukaryotic cells utilize macroautophagy (hereafter autophagy) to recycle cellular materials during nutrient stress. Target of rapamycin (Tor) is a central regulator of this process, acting by post-translational mechanisms, phosphorylating preformed autophagy-related (Atg) proteins to repress autophagy during log-phase growth. A role for this regulatory process in fungal virulence was further demonstrated by showing that overexpression of the Dcp2-associated mRNA-binding protein Vad1 in the AIDS-associated pathogen Cryptococcus neoformans results in constitutive repression of autophagy even under starvation conditions as well as attenuated virulence in a mouse model. In summary, Tor-dependent post-transcriptional regulation of autophagy plays a key role in the facilitation of microbial pathogenesis.

The many facets of homologous recombination at telomeres

Clémence Claussin and Michael Chang

The ends of linear chromosomes are capped by nucleoprotein structures called telomeres. A dysfunctional telomere may resemble a DNA double-strand break (DSB), which is a severe form of DNA damage. The presence of one DSB is sufficient to drive cell cycle arrest and cell death. Therefore cells have evolved mechanisms to repair DSBs such as homologous recombination (HR). HR-mediated repair of telomeres can lead to genome instability, a hallmark of cancer cells, which is why such repair is normally inhibited. However, some HR-mediated processes are required for proper telomere function. The need for some recombination activities at telomeres but not others necessitates careful and complex regulation, defects in which can lead to catastrophic consequences. Furthermore, some cell types can maintain telomeres via telomerase-independent, recombination-mediated mechanisms. In humans, these mechanisms...

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Groupthink: chromosomal clustering during transcriptional memory

Kevin A. Morano

In this article, the authors comment on the study "NO1 transcriptional memory leads to DNA zip code-dependent interchromosomal clustering." by Brickner et al. (Microbial Cell, 2015), discussing the importance and molecular mechanisms of chromosomal clustering during transcriptional memory.

Yeast proteinopathy models: a robust tool for deciphering the basis of neurodegeneration

Amit Shrestha1, 2 and Lynn A. Megeney1, 2, 3

Protein quality control or proteostasis is an essential determinant of basic cell health and aging. Eukaryotic cells have evolved a number of proteostatic mechanisms to ensure that proteins retain functional conformation, or are rapidly degraded when proteins misfold or self-aggregate. This article discusses the use of budding yeast as a robust proxy to study the intersection between proteostasis and neurodegenerative disease.

Starting with a degron: N-terminal formyl-methionine of nascent bacterial proteins contributes to their proteolytic control

R. Jürgen Dohmen

In this article, the author comments on the study "Formyl-methionine as a degradation signal at the N-termini of bacterial proteins." by Piatkov et al. (Microbial Cell, 2015), discussing a novel N-terminal degradation signal (N-degron) that targets nascent proteins for degradation in Escherichia coli by a new branch of the bacterial N-end rule pathway, termed the fMet/N-end rule pathway

Elongation factor-P at the crossroads of the host-endosymbiont interface

Andrei Rajkovic1, Anne Witzky2, William Navarre3, Andrew J. Darwin4 and Michael Ibba5

Elongation factor P (EF-P) is an ancient bacterial translational factor that aids the ribosome in polymerizing oligo-prolines. EF-P structurally resembles tRNA and binds in-between the exit and peptidyl sites of the ribosome to accelerate the intrinsically slow reaction of peptidyl-prolyl bond formation. Recent studies have identified in separate organisms, two evolutionarily convergent EF-P post-translational modification systems (EPMS), split predominantly between gammaproteobacteria, and betaproteobacteria. Here, the authors highlight the recent discoveries made regarding EPMSs, with a focus on how these incomplete modification pathways shape or have been shaped by the endosymbiont-host relationship.

Feelin’ it: Differential oxidative stress sensing mediated by Cyclin C

W. Scott Moye-Rowley

Microbial cells that live exposed directly to their environmental milieu are faced with the challenge of adapting to the dynamic stress conditions that will inevitably be encountered. These stress conditions may vary over wide ranges and the most efficient responses would be tuned to produce a proportional buffering change. A mild stress would most efficiently be dealt with by a mild metabolic reprogramming that would prevent serious damage. A more severe environmental challenge would demand a more dramatic cellular compensatory response.

Subverting lysosomal function in Trypanosoma brucei

Sam Alsford

This article discusses Koh et al. (2015) "The lysosomotropic drug LeuLeu-OMe induces lysosome disruption and autophagy-independent cell death in Trypanosoma brucei (Microbial Cell 2(8): 288-298).

Toxoplasma control of host apoptosis: the art of not biting too hard the hand that feeds you

Sébastien Besteiro

Toxoplasma gondii is an obligate intracellular parasite that is able to infect a multitude of different vertebrate hosts and can survive in virtually any nucleated cell. Here, the authors discuss the article "Toxoplasma gondii inhibits cytochrome c-induced caspase activation in its host cell by interference with holo-apoptosome assembly" by Graumann et al. (2015, Microbial Cell).

A safety catch for ornithine decarboxylase degradation

Christof Taxis

Feedback inhibition is a common mechanism to adjust the activity of an enzyme in accordance with the abundance of a product. This article comments on the study "Polyamines directly promote antizyme-mediated degradation of ornithine decarboxylase by the proteasome" by Beenukumar et al. (2015), Microbial Cell.

Fancy a gene? A surprisingly complex evolutionary history of peroxiredoxins.

Alena Zíková1,2, Miroslav Oborník1,2,3 and Julius Lukeš1,2,4

In this comment, the authors discuss the article "Prokaryotic ancestry and gene fusion of a dual localized peroxiredoxin in malaria parasites" (Djuika et al., Microbial Cell 2015).

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Groupthink: chromosomal clustering during transcriptional memory

November 26, 2015

In this article, the authors comment on the study "NO1 transcriptional memory leads to DNA zip code-dependent interchromosomal clustering." by Brickner et al. (Microbial Cell, 2015), discussing the importance and molecular mechanisms of chromosomal clustering during transcriptional memory.

Yeast proteinopathy models: a robust tool for deciphering the basis of neurodegeneration

November 26, 2015

Protein quality control or proteostasis is an essential determinant of basic cell health and aging. Eukaryotic cells have evolved a number of proteostatic mechanisms to ensure that proteins retain functional conformation, or are rapidly degraded when proteins misfold or self-aggregate. This article discusses the use of budding yeast as a robust proxy to study the intersection between proteostasis and neurodegenerative disease.

INO1 transcriptional memory leads to DNA zip code-dependent interchromosomal clustering

November 13, 2015

Many genes localize at the nuclear periphery through physical interaction with the nuclear pore complex (NPC). We have found that the yeast INO1 gene is targeted to the NPC both upon activation and for several generations after repression, a phenomenon called epigenetic transcriptional memory. Targeting of INO1 to the NPC requires distinct cis-acting promoter DNA zip codes under activating conditions and under memory conditions. When at the nuclear periphery, active INO1 clusters with itself and with other genes that share the GRS I zip code. Here, we show that during memory, the two alleles of INO1 cluster in diploids and endogenous INO1 clusters with an ectopic INO1 in haploids. After repression, INO1 does not cluster with GRS I - containing genes. Furthermore, clustering during memory requires Nup100 and two sets of DNA zip codes...

A central role for TOR signalling in a yeast model for juvenile CLN3 disease

November 11, 2015

Yeasts provide an excellent genetically tractable eukaryotic system for investigating the function of genes in their biological context, and are especially relevant for those conserved genes that cause disease. Bond et al. study the role of btn1, the orthologue of a human gene that underlies an early onset neurodegenerative disease (juvenile CLN3 disease, neuronal ceroid lipofuscinosis (NCLs) or Batten disease) in the fission yeast Schizosaccharomyces pombe.

Histone deacetylases: revealing the molecular base of dimorphism in pathogenic fungi

November 4, 2015

Fungi, as every living organism, interact with the external world and have to adapt to its fluctuations. For pathogenic fungi, such interaction involves adapting to the hostile environment of their host. Survival depends on the capacity of fungi to detect and respond to external stimuli, which is achieved through a tight and efficient genetic control. Elías-Villalobos et al. propose that histone acetylation is critical to the proper timing and induction of transcription of the genes encoding factors that coordinate changes in morphology with pathogenesis.

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.

Oxygen availability strongly affects chronological lifespan and thermotolerance in batch cultures of Saccharomyces cerevisiae

October 22, 2015

Stationary-phase (SP) batch cultures of Saccharomyces cerevisiae, in which growth has been arrested by carbon-source depletion, are widely applied to study chronological lifespan, quiescence and SP-associated robustness. Based on this type of experiments, typically performed under aerobic conditions, several roles of oxygen in aging have been proposed. However, SP in anaerobic yeast cultures has not been investigated in detail. Here, we use the unique capability of S. cerevisiae to grow in the complete absence of oxygen to directly compare SP in aerobic and anaerobic bioreactor cultures. This comparison revealed strong positive effects of oxygen availability on adenylate energy charge, longevity and thermotolerance during SP. A low thermotolerance of...

Electron microscopy for ultrastructural analysis and protein localization in Saccharomyces cerevisiae

October 12, 2015

The yeast Saccharomyces cerevisiae is a key model system for studying of a multitude of cellular processes because of its amenability to genetics, molecular biology and biochemical procedures. The goal of this review is to guide researchers that want to investigate a particular process at the ultrastructural level in yeast by aiding in the selection of the most appropriate approach to visualize a specific structure or subcellular compartment.

Starting with a degron: N-terminal formyl-methionine of nascent bacterial proteins contributes to their proteolytic control

October 4, 2015

In this article, the author comments on the study "Formyl-methionine as a degradation signal at the N-termini of bacterial proteins." by Piatkov et al. (Microbial Cell, 2015), discussing a novel N-terminal degradation signal (N-degron) that targets nascent proteins for degradation in Escherichia coli by a new branch of the bacterial N-end rule pathway, termed the fMet/N-end rule pathway

A bacterial volatile signal for biofilm formation

September 23, 2015

Bacteria constantly monitor the environment they reside in and respond to potential changes in the environment through a variety of signal sensing and transduction mechanisms in a timely fashion. In their recent study (Chen, et al. mBio (2015), 6: e00392-15), the authors demonstrated that the soil bacterium Bacillus subtilis uses acetic acid as a volatile signal to coordinate the timing of biofilm formation within physically separated cells in the community. They also showed that the bacterium possesses an intertwined gene network to produce, secrete, sense, and respond to acetic acid, in stimulating biofilm formation.

Next