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

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Abstract

The experimental evidence from the last decade made telomerase a prominent member of a family of moonlighting proteins performing different functions at various cellular loci. However, the study of extratelomeric functions of the catalytic subunit of mammalian telomerase (TERT) is often complicated by the fact that it is sometimes difficult to distinguish them from its role(s) at the chromosomal ends. Here, we present an experimental model for studying the extranuclear function(s) of mammalian telomerase in the yeast Saccharomyces cerevisiae. We demonstrate that the catalytic subunit of mammalian telomerase protects the yeast cells against oxidative stress and affects the stability of the mitochondrial genome. The advantage of using S. cerevisiae to study of mammalian telomerase is that (1) mammalian TERT does not interfere with its yeast counterpart in the maintenance of telomeres, (2) yeast telomerase is not localized in mitochondria and (3) it does not seem to be involved in the protection of cells against oxidative stress and stabilization of mtDNA. Thus, yeast cells can be used as a ‘test tube’ for reconstitution of mammalian TERT extranuclear function(s).

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Acknowledgments

We thank Ladislav Kovac for inspiration and continuous support, H. Yde Steensma (Leiden University, The Netherlands) for the S. cerevisiae strain GG595, Johannes H. Hegemann (Heinrich-Heine-Universität, Düsseldorf, Germany) for the plasmid pUG35-yEGFP3, Ronald A. DePinho (University of Texas, USA) for the plasmid pGRN188, Juraj Kramara (Palacky University in Olomouc, Czech republic) for technical assistance and Jiri Bartek (Palacky University in Olomouc, Czech republic) for providing the possibility to perform fluorescent microscopy in his laboratory. We also thank two anonymous reviewers for their constructive comments, which helped us to improve the manuscript. This work was supported in part by the Slovak grant agencies APVV (0035-11 and 0123-10), VEGA (1/0311/12) and Comenius University (UK/409/2014) and National Institutes of Health Grants 2R01ES013773-06A1.

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The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Genetics, Faculty of Natural Sciences, Comenius University, Mlynska dolina, B-1, 84215, Bratislava, Slovak Republic

    Lucia Simonicova, Henrieta Dudekova, Jaroslav Ferenc, Katarina Prochazkova, Roman Dusinsky & Lubomir Tomaska

  2. Department of Biochemistry, Faculty of Natural Sciences, Comenius University, Mlynska dolina, CH-1, 84215, Bratislava, Slovak Republic

    Martina Nebohacova & Jozef Nosek

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  1. Lucia Simonicova
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  2. Henrieta Dudekova
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Correspondence to Lubomir Tomaska.

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Communicated by S. Hohmann.

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Simonicova, L., Dudekova, H., Ferenc, J. et al. Saccharomyces cerevisiae as a model for the study of extranuclear functions of mammalian telomerase. Curr Genet 61, 517–527 (2015). https://doi.org/10.1007/s00294-014-0472-8

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