Environmental stresses disrupt telomere length homeostasis

Gal Hagit Romano; Yaniv Harari; Tal Yehuda; Ariel Podhorzer; Linda Rubinstein; Ron Shamir; Assaf Gottlieb; Yael Silberberg; Dana Pe'er; Eytan Ruppin; Roded Sharan; Martin Kupiec

doi:10.1371/journal.pgen.1003721

Environmental stresses disrupt telomere length homeostasis

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

Authors

Gal Hagit Romano¹, Yaniv Harari, Tal Yehuda, Ariel Podhorzer, Linda Rubinstein, Ron Shamir, Assaf Gottlieb, Yael Silberberg, Dana Pe'er, Eytan Ruppin, Roded Sharan, Martin Kupiec

Affiliation

¹ Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Tel Aviv, Israel ; Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel ; Department of Biological Sciences, Columbia University, New York, New York, United States of America.

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*
Shelterin Complex
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
Shelterin Complex
Telomere-Binding Proteins
Transcription Factors
Acetic Acid

Grants and funding

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.