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

Curr Genet. 2015 Nov;61(4):517-27. doi: 10.1007/s00294-014-0472-8. Epub 2015 Jan 8.

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).

Keywords: Mitochondria; Oxidative stress; Telomerase; Yeast.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Catalytic Domain / genetics
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Fusarium / drug effects
  • Fusarium / genetics
  • Fusarium / metabolism
  • Gene Expression Regulation, Fungal*
  • Genetic Engineering
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Models, Biological
  • Neurospora crassa / drug effects
  • Neurospora crassa / genetics
  • Neurospora crassa / metabolism
  • Oxidative Stress
  • Plasmids / chemistry
  • Plasmids / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Telomerase / genetics*
  • Telomerase / metabolism
  • Telomere / metabolism*
  • Telomere / ultrastructure
  • Transformation, Genetic
  • Vitamin K 3 / pharmacology

Substances

  • DNA, Mitochondrial
  • Forkhead Transcription Factors
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • mesenchyme fork head 1 protein
  • Vitamin K 3
  • EST2 protein, S cerevisiae
  • Telomerase
  • Tert protein, mouse