Saccharomyces cerevisiae as a model for the study of extranuclear functions of mammalian telomerase

Simonicova, Lucia; Dudekova, Henrieta; Ferenc, Jaroslav; Procházková, Katarína; Neboháčová, Martina; Dušinský, Roman; Nosek, Jozef; Tomáška, Ľubomír

doi:10.1007/s00294-014-0472-8

Cited by 10 publications

(7 citation statements)

References 66 publications

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“…Simple organisms such as budding and fission yeast have contributed enormously to our understanding of telomere biology (Simonicova et al 2015;Millet and Makovets 2016;Gadaleta et al 2016). A number of studies in Saccharomyces cerevisiae identified mutants that affect telomere length.…”

Section: Sus1 Interacts Physically and Genetically With Genes Affectimentioning

confidence: 99%

“…Yeast cells provide an excellent model to study mechanisms that affect telomere biology (Askree et al 2004;Simonicova et al 2015;Machin et al 2016;Millet and Makovets 2016;Gadaleta et al 2016). Proteins located at the nuclear periphery in close proximity to TREX-2 have been implicated in genome integrity by protecting the telomeric repeats from recombination.…”

Section: Introductionmentioning

confidence: 99%

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The evolutionarily conserved factor Sus1/ENY2 plays a role in telomere length maintenance

et al. 2017

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Sus1 is a conserved protein involved in histone H2B de-ubiquitination and mRNA export from the nucleus in eukaryotes. Previous studies implicated Sus1 partners in genome integrity including telomere homeostasis. However, the implication of Sus1 in telomere maintenance remains largely unknown. In this study, we found that yeast Sus1 interacts physically and genetically with factors involved in telomere maintenance and its absence leads to elongated telomeres. Deletion of several of Sus1's partners also leads to longer telomeres. Our results rule out a direct role for Sus1 in recruiting telomerase subunits to telomeres. However, we observe that deletion of SUS1 leads to elongated telomeres even in the presence of mutations like sem1Δ, esc2Δ and rsc2Δ, which cause telomere shortening. We find that rsc2Δ (short telomeres) have reduced levels of mono-ubiquitinated histone H2B at lysine 123 (H2BK123ub), whereas sus1Δ mutants or double-mutants sus1Δ rsc2Δ exhibit longer telomeres and higher H2BK123ub levels. These results suggest that Sus1 activity as a H2B de-ubiquitination modulator plays a role in negatively regulating telomere length. Our results provide solid evidence for a role of Sus1 in negatively regulating telomere length through the modulation of H2BK123 mono-ubiquitination and its interaction with the nuclear pore complex.

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Section: Sus1 Interacts Physically and Genetically With Genes Affectimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The evolutionarily conserved factor Sus1/ENY2 plays a role in telomere length maintenance

et al. 2017

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“…Their disparate canonical functions and the wide range of moonlighting activities are astonishing and show the power of evolution to produce new functions from extant materials. The biochemical and genetic potentialities of yeasts emphasize their importance in studying moonlighting functions, not only of yeast proteins but also of proteins from other organisms, as shown by Simonicova et al (104), who used S. cerevisiae to study extratelomeric functions of mammalian telomerase.…”

Section: Final Remarks and Perspectivesmentioning

confidence: 99%

The Expanding Landscape of Moonlighting Proteins in Yeasts

Gancedo

Flores

Gancedo

2016

Microbiol Mol Biol Rev

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SUMMARYMoonlighting proteins are multifunctional proteins that participate in unrelated biological processes and that are not the result of gene fusion. A certain number of these proteins have been characterized in yeasts, and the easy genetic manipulation of these microorganisms has been useful for a thorough analysis of some cases of moonlighting. As the awareness of the moonlighting phenomenon has increased, a growing number of these proteins are being uncovered. In this review, we present a crop of newly identified moonlighting proteins from yeasts and discuss the experimental evidence that qualifies them to be classified as such. The variety of moonlighting functions encompassed by the proteins considered extends from control of transcription to DNA repair or binding to plasminogen. We also discuss several questions pertaining to the moonlighting condition in general. The cases presented show that yeasts are important organisms to be used as tools to understand different aspects of moonlighting proteins.

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“…(reviewed in Gasch 2007 ). Mammalian telomerase expressed in yeast has also been suggested to protect their genome from oxidative stress (Simonicova et al 2015 ). How much do chromosome VIII aneuploids resemble cells with ESR activated?…”

Section: Resultsmentioning

confidence: 99%

Aneuploidy as a mechanism of adaptation to telomerase insufficiency

Millet

Makovets

2016

Curr Genet

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Cells’ survival is determined by their ability to adapt to constantly changing environment. Adaptation responses involve global changes in transcription, translation, and posttranslational modifications of proteins. In recent years, karyotype changes in adapting populations of single cell organisms have been reported in a number of studies. More recently, we have described aneuploidy as an adaptation mechanism used by populations of budding yeast Saccharomyces cerevisiae to survive telomerase insufficiency induced by elevated growth temperature. Genetic evidence suggests that telomerase insufficiency is caused by decreased levels of the telomerase catalytic subunit Est2. Here, we present experiments arguing that the underlying cause of this phenomenon may be within the telomerase RNA TLC1: changes in the expression of TLC1 as well as mutations in the TLC1 template region affect telomere length equilibrium and the temperature threshold for the induction of telomerase insufficiency. We discuss what lies at the root of telomerase insufficiency, how cell populations overcome it through aneuploidy and whether reversible aneuploidy could be an adaptation mechanism for a variety of environmental stresses.

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Saccharomyces cerevisiae as a model for the study of extranuclear functions of mammalian telomerase

Cited by 10 publications

References 66 publications

The evolutionarily conserved factor Sus1/ENY2 plays a role in telomere length maintenance

The evolutionarily conserved factor Sus1/ENY2 plays a role in telomere length maintenance

The Expanding Landscape of Moonlighting Proteins in Yeasts

Aneuploidy as a mechanism of adaptation to telomerase insufficiency

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