Deletion of the major peroxiredoxin Tsa1 alters telomere length homeostasis

Jian Lu, Haritha Vallabhaneni, Jinhu Yin, Yie Liu

Research output: Contribution to journalArticlepeer-review

Abstract

Reactive oxygen species (ROS) are proposed to play a major role in telomere length alterations during aging. The mechanisms by which ROS disrupt telomeres remain unclear. In Saccharomyces cerevisiae, telomere DNA consists of TG(1-3) repeats, which are maintained primarily by telomerase. Telomere length maintenance can be modulated by the expression level of telomerase subunits and telomerase activity. Additionally, telomerase-mediated telomere repeat addition is negatively modulated by the levels of telomere-bound Rap1-Rif1-Rif2 protein complex. Using a yeast strain defective in the major peroxiredoxin Tsa1 that is involved in ROS neutralization, we have investigated the effect of defective ROS detoxification on telomere DNA, telomerase, telomere-binding proteins, and telomere length. Surprisingly, the tsa1 mutant does not show significant increase in steady-state levels of oxidative DNA lesions at telomeres. The tsa1 mutant displays abnormal telomere lengthening, and reduction in oxidative exposure alleviates this phenotype. The telomere lengthening in the tsa1 cells was abolished by disruption of Est2, subtelomeric DNA, Rap1 C-terminus, or Rif2, but not by Rif1 deletion. Although telomerase expression and activity are not altered, telomere-bound Est2 is increased, while telomere-bound Rap1 is reduced in the tsa1 mutant. We propose that defective ROS scavenging can interfere with pathways that are critical in controlling telomere length homeostasis. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Original languageEnglish (US)
Pages (from-to)635-644
Number of pages10
JournalAging Cell
Volume12
Issue number4
DOIs
StatePublished - Aug 2013

Keywords

  • Peroxiredoxin
  • Reactive oxygen species
  • Telomerase
  • Telomere length

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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