Environmental stresses disrupt telomere length homeostasis

PLoS Genet. 2013;9(9):e1003721. doi: 10.1371/journal.pgen.1003721. Epub 2013 Sep 5.

Abstract

Telomeres protect the chromosome ends from degradation and play crucial roles in cellular aging and disease. Recent studies have additionally found a correlation between psychological stress, telomere length, and health outcome in humans. However, studies have not yet explored the causal relationship between stress and telomere length, or the molecular mechanisms underlying that relationship. Using yeast as a model organism, we show that stresses may have very different outcomes: alcohol and acetic acid elongate telomeres, whereas caffeine and high temperatures shorten telomeres. Additional treatments, such as oxidative stress, show no effect. By combining genome-wide expression measurements with a systematic genetic screen, we identify the Rap1/Rif1 pathway as the central mediator of the telomeric response to environmental signals. These results demonstrate that telomere length can be manipulated, and that a carefully regulated homeostasis may become markedly deregulated in opposing directions in response to different environmental cues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetic Acid / pharmacology
  • Alcohols / pharmacology
  • Chromosomes, Fungal / drug effects
  • Chromosomes, Fungal / metabolism
  • Gene-Environment Interaction
  • Homeostasis / drug effects
  • Homeostasis / genetics
  • Humans
  • Oxidative Stress / genetics
  • Oxidative Stress / physiology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae Proteins / genetics*
  • Stress, Physiological*
  • Telomere / drug effects
  • Telomere / genetics*
  • Telomere Homeostasis / drug effects
  • Telomere Homeostasis / genetics*
  • Telomere-Binding Proteins / genetics*
  • Telomere-Binding Proteins / metabolism
  • Transcription Factors / genetics*

Substances

  • Alcohols
  • RAP1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Telomere-Binding Proteins
  • Transcription Factors
  • Acetic Acid

Grant support

MK was supported by grants from the Israel Ministry of Science and Technology, the Israel Cancer Research Fund and the Israel Cancer Foundation. GHR was supported by the Machiah foundation and by the Safra Center for Bioinformatics. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.