Saccharomyces cerevisiae as a Model System for Eukaryotic Cell Biology, from Cell Cycle Control to DNA Damage Response

Vanderwaeren, Laura; Dok, Rüveyda; Voordeckers, Karin; Nuyts, Sandra; Verstrepen, Kevin J.

doi:10.3390/ijms231911665

Cited by 27 publications

(14 citation statements)

References 233 publications

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“…S. cerevisiae is an excellent model organism to study various aspects of DNA damage response, DNA repair pathways, and mechanisms of DNA damage induction by chemical agents [ 97 – 99 ]. Studies using either wild-type yeast or mutants devoid of As(III)/Sb(III) detoxification transporters Acr3 and Ycf1 revealed that both As(III) and Sb(III) exhibit genotoxic properties at subcytotoxic concentrations [ 62 , 68 ].…”

Section: How Arsenic and Antimony Cause Genotoxicitymentioning

confidence: 99%

“…Studies using either wild-type yeast or mutants devoid of As(III)/Sb(III) detoxification transporters Acr3 and Ycf1 revealed that both As(III) and Sb(III) exhibit genotoxic properties at subcytotoxic concentrations [ 62 , 68 ]. 1 h exposure to As(III) triggered phosphorylation of histone H2A on Ser129 (an equivalent of human γH2AX, which is a sensitive DNA damage marker also in yeast) [ 97 – 99 ], starting from 250 μM in wild type and 50 μM in the double mutant acr3 Δ ycf1 Δ [ 62 , 68 ]. For Sb(III), high levels of H2A phosphorylation were observed after 1–2 h treatment with 200–500 μM in ycf1 Δ cells [ 62 , 68 ].…”

Section: How Arsenic and Antimony Cause Genotoxicitymentioning

confidence: 99%

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Mechanisms of genotoxicity and proteotoxicity induced by the metalloids arsenic and antimony

Wysocki,

Rodrigues,

Litwin

et al. 2023

Cell. Mol. Life Sci.

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Arsenic and antimony are metalloids with profound effects on biological systems and human health. Both elements are toxic to cells and organisms, and exposure is associated with several pathological conditions including cancer and neurodegenerative disorders. At the same time, arsenic- and antimony-containing compounds are used in the treatment of multiple diseases. Although these metalloids can both cause and cure disease, their modes of molecular action are incompletely understood. The past decades have seen major advances in our understanding of arsenic and antimony toxicity, emphasizing genotoxicity and proteotoxicity as key contributors to pathogenesis. In this review, we highlight mechanisms by which arsenic and antimony cause toxicity, focusing on their genotoxic and proteotoxic effects. The mechanisms used by cells to maintain proteostasis during metalloid exposure are also described. Furthermore, we address how metalloid-induced proteotoxicity may promote neurodegenerative disease and how genotoxicity and proteotoxicity may be interrelated and together contribute to proteinopathies. A deeper understanding of cellular toxicity and response mechanisms and their links to pathogenesis may promote the development of strategies for both disease prevention and treatment.

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Section: How Arsenic and Antimony Cause Genotoxicitymentioning

confidence: 99%

Section: How Arsenic and Antimony Cause Genotoxicitymentioning

confidence: 99%

Mechanisms of genotoxicity and proteotoxicity induced by the metalloids arsenic and antimony

Wysocki,

Rodrigues,

Litwin

et al. 2023

Cell. Mol. Life Sci.

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“…One non‐pathogenic yeast species in particular, Saccharomyces cerevisiae (budding yeast), is commonly used as a powerful model to uncover the molecular machinery responsible for fundamental processes underlying diverse eukaryotic biology, for example, cell cycle, autophagy, membrane trafficking, the ubiquitin–proteasome system, and so forth. (Finley et al., 2012 ; Feyder et al., 2015 ; Zimmerman et al., 2016 ; Vanderwaeren et al., 2022 ). Notably, budding yeast was used to discover ESCRTs (endosomal sorting complexes required for transport) and ALIX responsible for biogenesis of a subclass of EVs called exosomes (Baietti et al., 2012 ; Gurung et al., 2021 ; Hurley, 2010 ; Juan & Fürthauer, 2018 ) and to uncover the molecular network responsible for preventing proteotoxicity induced by heat stress (i.e., the heat shock response; Lindquist & Craig, 1988 ).…”

Section: Introductionmentioning

confidence: 99%

Thermotolerance in S. cerevisiae as a model to study extracellular vesicle biology

Logan,

Staton,

Oliver

et al. 2024

J of Extracellular Vesicle

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The budding yeast Saccharomyces cerevisiae is a proven model organism for elucidating conserved eukaryotic biology, but to date its extracellular vesicle (EV) biology is understudied. Here, we show yeast transmit information through the extracellular medium that increases survival when confronted with heat stress and demonstrate the EV‐enriched samples mediate this thermotolerance transfer. These samples contain vesicle‐like particles that are exosome‐sized and disrupting exosome biogenesis by targeting endosomal sorting complexes required for transport (ESCRT) machinery inhibits thermotolerance transfer. We find that Bro1, the yeast ortholog of the human exosome biomarker ALIX, is present in EV samples, and use Bro1 tagged with green fluorescent protein (GFP) to track EV release and uptake by endocytosis. Proteomics analysis reveals that heat shock protein 70 (HSP70) family proteins are enriched in EV samples that provide thermotolerance. We confirm the presence of the HSP70 ortholog stress‐seventy subunit A2 (Ssa2) in EV samples and find that mutant yeast cells lacking SSA2 produce EVs but they fail to transfer thermotolerance. We conclude that Ssa2 within exosomes shared between yeast cells contributes to thermotolerance. Through this work, we advance Saccharomyces cerevisiae as an emerging model organism for elucidating molecular details of eukaryotic EV biology and establish a role for exosomes in heat stress and proteostasis that seems to be evolutionarily conserved.

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“…2 h). They are extensively used as a model system for the wide type of eukaryotic cell biology studies (from cell cycle control to DNA damage response) [ 20 ]. They also do not raise ethical doubts compared to animal research.…”

Section: Introductionmentioning

confidence: 99%

Adsorption of Zearalenone by Aureobasidium pullulans Autolyzed Biomass Preparation and Its Detoxification Properties in Cultures of Saccharomyces cerevisiae Yeast

Bzducha-Wróbel,

Janowicz,

Bryła

et al. 2024

Toxins

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Different preventive strategies are needed to minimize the intake risks of mycotoxins, including zearalenone (ZEN). The aim of this study was to determine the ZEN adsorption ability of an autolyzed biomass preparation of polymorphic yeast Aureobasidium pullulans A.p.-3. The evaluation of the antitoxic properties of the preparation was also performed in relation to Saccharomyces cerevisiae yeast (ATCC 2366, ATCC 7090 and ATCC 9763) used as a model cell exposed to a toxic ZEN dose. The preparation at a dose of 5 mg/mL showed the adsorption of ZEN present in model systems at concentrations between 1 μg/mL to 100 μg/mL. The highest degree of adsorption was established for ZEN concentrations of 1 μg/mL and 5 μg/mL, becoming limited at higher doses of the toxin. Based on the Langmuir model of adsorption isotherms, the predicted maximum ZEN adsorption was approx. 190 µg/mL, regardless of pH. The growth of three strains of S. cerevisiae yeast cells in the medium with ZEN at concentrations within the range of 1.56 μg/mL–100 μg/mL was analyzed to determine the minimum inhibitory concentration. The growth of all tested strains was especially limited by high doses of ZEN, i.e., 50 and 100 μg/mL. The protective effect of the tested preparation was noted in relation to yeast cells exposed to toxic 100 μg/mL ZEN doses. The highest yeast cell growth (app. 36% percentage) was noted for a S. cerevisiae ATCC 9763 strain compared to the medium with ZEN but without preparation. More detailed tests determining the antitoxic mechanisms of the A. pullulans preparation are planned in the future, including cell culture bioassays and animal digestive tract models.

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Saccharomyces cerevisiae as a Model System for Eukaryotic Cell Biology, from Cell Cycle Control to DNA Damage Response

Cited by 27 publications

References 233 publications

Mechanisms of genotoxicity and proteotoxicity induced by the metalloids arsenic and antimony

Mechanisms of genotoxicity and proteotoxicity induced by the metalloids arsenic and antimony

Thermotolerance in S. cerevisiae as a model to study extracellular vesicle biology

Adsorption of Zearalenone by Aureobasidium pullulans Autolyzed Biomass Preparation and Its Detoxification Properties in Cultures of Saccharomyces cerevisiae Yeast

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