title: Deletion of the major peroxiredoxin Tsa1 alters telomere length homeostasis.
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.
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 251 Bayview Drive, Baltimore, MD 21224-6825, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Lu
authors.forename: Haritha
authors.initials: H
authors.lastname: Vallabhaneni
authors.forename: Jinhu
authors.initials: J
authors.lastname: Yin
authors.forename: Yie
authors.initials: Y
authors.lastname: Liu
mesh_terms: D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D000089804:Shelterin Complex; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D059505:Telomere Homeostasis; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004271:DNA, Fungal; C440829:RAP1 protein, S cerevisiae; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D014157:Transcription Factors; C074461:RIF1 protein, S cerevisiae; D010544:Peroxidases; C496253:Tsa1 protein, S cerevisiae; D019098:Telomerase
keywords: peroxiredoxin; reactive oxygen species; telomerase; telomere length