Cell populations can use aneuploidy to survive telomerase insufficiency.
Telomerase maintains ends of eukaryotic chromosomes, telomeres. Telomerase loss results in replicative senescence and a switch to recombination-dependent telomere maintenance. Telomerase insufficiency in humans leads to telomere syndromes associated with premature ageing and cancer predisposition. Here we use yeast to show that the survival of telomerase insufficiency differs from the survival of telomerase loss and occurs through aneuploidy. In yeast grown at elevated temperatures, telomerase activity becomes limiting: haploid cell populations senesce and generate aneuploid survivors--near diploids monosomic for chromosome VIII. This aneuploidy results in increased levels of the telomerase components TLC1, Est1 and Est3, and is accompanied by decreased abundance of ribosomal proteins. We propose that aneuploidy suppresses telomerase insufficiency through redistribution of cellular resources away from ribosome synthesis towards production of telomerase components and other non-ribosomal proteins. The aneuploidy-induced re-balance of the proteome via modulation of ribosome biogenesis may be a general adaptive response to overcome functional insufficiencies.
Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FF, UK.
Caroline
C
Millet
Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FF, UK.
Darya
D
Ausiannikava
Centre for Synthetic and Systems Biology (SynthSys), School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JD, UK.
Thierry
T
Le Bihan
Centre for Synthetic and Systems Biology (SynthSys), School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JD, UK.
Sander
http://orcid.org/0000-0003-4387-1271
S
Granneman
Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FF, UK.
Svetlana
S
Makovets
D000782:Aneuploidy; D016922:Cellular Senescence / Q000235:genetics; D004171:Diploidy; D006238:Haploidy; D012313:RNA / Q000235:genetics; D012269:Ribosomal Proteins; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D019098:Telomerase / Q000172:deficiency / Q000235:genetics*; D059505:Telomere Homeostasis
D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; C422952:telomerase RNA; D012313:RNA; C099024:EST1 protein, S cerevisiae; C491580:EST3 protein, S cerevisiae; D019098:Telomerase