The genome-wide transcription response to telomerase deficiency in the thermotolerant yeast Hansenula polymorpha DL-1

Alexey V. Beletsky, Alexander N. Malyavko, Maria V. Sukhanova, Eugenia S. Mardanova, Maria I. Zvereva, Olga A. Petrova, Yulia Yu Parfenova, Maria P. Rubtsova, Andrey V. Mardanov, Olga I. Lavrik, Olga A. Dontsova, Nikolai V. Ravin

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Background: In the course of replication of eukaryotic chromosomes, the telomere length is maintained due to activity of telomerase, the ribonucleoprotein reverse transcriptase. Abolishing telomerase function causes progressive shortening of telomeres and, ultimately, cell cycle arrest and replicative senescence. To better understand the cellular response to telomerase deficiency, we performed a transcriptomic study for the thermotolerant methylotrophic yeast Hansenula polymorpha DL-1 lacking telomerase activity. Results: Mutant strain of H. polymorpha carrying a disrupted telomerase RNA gene was produced, grown to senescence and analyzed by RNA-seq along with wild type strain. Telomere shortening induced a transcriptional response involving genes relevant to telomere structure and maintenance, DNA damage response, information processing, and some metabolic pathways. Genes involved in DNA replication and repair, response to environmental stresses and intracellular traffic were up-regulated in senescent H. polymorpha cells, while strong down-regulation was observed for genes involved in transcription and translation, as well as core histones. Conclusions: Comparison of the telomerase deletion transcription responses by Saccharomyces cerevisiae and H. polymorpha demonstrates that senescence makes different impact on the main metabolic pathways of these yeast species but induces similar changes in processes related to nucleic acids metabolism and protein synthesis. Up-regulation of a subunit of the TORC1 complex is clearly relevant for both types of yeast.

Original languageEnglish
Article number492
Pages (from-to)492
Number of pages12
JournalBMC Genomics
Volume18
Issue number1
DOIs
Publication statusPublished - 28 Jun 2017

Keywords

  • Autophagy
  • DNA repair
  • Environmental stress response
  • Hansenula polymorpha
  • RNA-seq
  • Senescence
  • Telomerase
  • Yeast
  • Carbohydrate Metabolism/genetics
  • DNA Damage/genetics
  • Genomics
  • Telomere Shortening/genetics
  • Energy Metabolism/genetics
  • Pichia/cytology
  • Genes, Fungal/genetics
  • RNA, Messenger/genetics
  • Autophagy/genetics
  • Stress, Physiological/genetics
  • Intracellular Space/metabolism
  • Environment
  • Transcription, Genetic
  • Thermotolerance
  • Telomerase/deficiency
  • DNA-DAMAGE RESPONSE
  • BINDING-PROTEIN
  • LENGTH REGULATION
  • SACCHAROMYCES-CEREVISIAE
  • BUDDING YEAST
  • DOUBLE-STRAND BREAKS
  • MAINTENANCE
  • INDUCED REPLICATION
  • UNCAPPED TELOMERES
  • CHROMOSOME END PROTECTION

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