title: Environmental stresses disrupt telomere length homeostasis.
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.
authors.affiliation: 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.
authors.forename: Gal Hagit
authors.initials: GH
authors.lastname: Romano
authors.forename: Yaniv
authors.initials: Y
authors.lastname: Harari
authors.forename: Tal
authors.initials: T
authors.lastname: Yehuda
authors.forename: Ariel
authors.initials: A
authors.lastname: Podhorzer
authors.forename: Linda
authors.initials: L
authors.lastname: Rubinstein
authors.forename: Ron
authors.initials: R
authors.lastname: Shamir
authors.forename: Assaf
authors.initials: A
authors.lastname: Gottlieb
authors.forename: Yael
authors.initials: Y
authors.lastname: Silberberg
authors.forename: Dana
authors.initials: D
authors.lastname: Pe'er
authors.forename: Eytan
authors.initials: E
authors.lastname: Ruppin
authors.forename: Roded
authors.initials: R
authors.lastname: Sharan
authors.forename: Martin
authors.initials: M
authors.lastname: Kupiec
mesh_terms: D019342:Acetic Acid / Q000494:pharmacology; D000438:Alcohols / Q000494:pharmacology; D015825:Chromosomes, Fungal / Q000187:drug effects / Q000378:metabolism; D059647:Gene-Environment Interaction; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics; D006801:Humans; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D000089804:Shelterin Complex; D013312:Stress, Physiological; D016615:Telomere / Q000187:drug effects / Q000235:genetics*; D059505:Telomere Homeostasis / Q000187:drug effects / Q000235:genetics*; D034501:Telomere-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D000438:Alcohols; C440829:RAP1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D014157:Transcription Factors; D019342:Acetic Acid
references.citation: Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14572-7
references.pmid: 21844336
references.citation: PLoS Genet. 2011 Apr;7(4):e1001362
references.pmid: 21490951
references.citation: Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):1911-4
references.pmid: 15665079
references.citation: J Immunol. 2007 Sep 15;179(6):4249-54
references.pmid: 17785865
references.citation: Nature. 2011 Jan 6;469(7328):102-6
references.pmid: 21113150
references.citation: Curr Biol. 2011 Dec 20;21(24):2115-20
references.pmid: 22169538
references.citation: Mol Biol Cell. 2000 Dec;11(12):4241-57
references.pmid: 11102521
references.citation: Science. 2009 Nov 13;326(5955):948-52
references.pmid: 19965504
references.citation: Genes Dev. 2007 Oct 1;21(19):2485-94
references.pmid: 17908934
references.citation: Mol Cell Biol. 2012 May;32(9):1604-17
references.pmid: 22354991
references.citation: Genes Dev. 1997 Feb 15;11(4):512-27
references.pmid: 9042864
references.citation: Nat Methods. 2008 Aug;5(8):711-8
references.pmid: 18622397
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8658-63
references.pmid: 15161972
references.citation: Nat Struct Mol Biol. 2004 Dec;11(12):1198-205
references.pmid: 15531893
references.citation: Mol Syst Biol. 2008;4:172
references.pmid: 18319724
references.citation: Mol Cell Biol. 1992 Nov;12(11):5159-73
references.pmid: 1406688
references.citation: Cell. 1989 May 19;57(4):633-43
references.pmid: 2655926
references.citation: EMBO Rep. 2007 Nov;8(11):1080-5
references.pmid: 17917674
references.citation: Soc Sci Med. 2012 Jun;74(12):1948-51
references.pmid: 22472277
references.citation: Curr Biol. 1998 May 21;8(11):657-60
references.pmid: 9635193
references.citation: J Cell Biol. 2006 Dec 4;175(5):825-35
references.pmid: 17145966
references.citation: Genes Dev. 1993 Apr;7(4):592-604
references.pmid: 8458576
references.citation: Curr Genet. 2005 Jan;47(1):18-28
references.pmid: 15551135
references.citation: Exp Cell Res. 1965 Mar;37:614-36
references.pmid: 14315085
references.citation: Nat Rev Genet. 2005 Aug;6(8):611-22
references.pmid: 16136653
references.citation: Oncogene. 2002 Jan 21;21(4):564-79
references.pmid: 11850781
references.citation: Genetics. 2012 May;191(1):79-93
references.pmid: 22377634
references.citation: Mol Cell Biol. 1998 Oct;18(10):6121-30
references.pmid: 9742129
references.citation: Mol Syst Biol. 2009;5:248
references.pmid: 19293828
references.citation: Curr Biol. 2001 Sep 4;11(17):1328-35
references.pmid: 11553325
references.citation: Nucleic Acids Res. 2009 Jul;37(12):3840-9
references.pmid: 19386622
references.citation: PLoS Genet. 2006 Mar;2(3):e35
references.pmid: 16552446
references.citation: Brain Behav Immun. 2010 May;24(4):531-9
references.pmid: 20018236
references.citation: Nat Struct Mol Biol. 2012 Feb 12;19(3):307-13
references.pmid: 22343724
references.citation: Nature. 2002 Jul 25;418(6896):387-91
references.pmid: 12140549
references.citation: PLoS One. 2012;7(3):e33498
references.pmid: 22448247
references.citation: Mol Cell. 2004 May 21;14(4):515-22
references.pmid: 15149600
references.citation: Nat Chem Biol. 2007 Oct;3(10):640-9
references.pmid: 17876321
references.citation: PLoS Genet. 2011 Dec;7(12):e1002417
references.pmid: 22194703
references.citation: Oncogene. 2002 Jan 21;21(4):553-63
references.pmid: 11850780
references.citation: Bioinformatics. 2006 Apr 15;22(8):943-9
references.pmid: 16473874
references.citation: Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12486-91
references.pmid: 9770512
references.citation: Nat Genet. 2005 Oct;37(10):1147-52
references.pmid: 16155567
references.citation: Aging Cell. 2007 Dec;6(6):769-74
references.pmid: 17925004
references.citation: Genes Dev. 1997 Mar 15;11(6):748-60
references.pmid: 9087429
references.citation: Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21
references.pmid: 11309499
references.citation: Cancer Res. 1999 Sep 1;59(17):4375-82
references.pmid: 10485486
references.citation: Genes Dev. 2012 Jan 15;26(2):137-50
references.pmid: 22279046
references.citation: Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11465-70
references.pmid: 20534547
references.citation: Nature. 2012 Feb 15;482(7385):363-8
references.pmid: 22337056
references.citation: Carcinogenesis. 2010 Jan;31(1):9-18
references.pmid: 19887512
references.citation: Appl Microbiol Biotechnol. 2010 Sep;88(1):231-9
references.pmid: 20661734
references.citation: Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17312-5
references.pmid: 15574496
references.citation: Nat Struct Mol Biol. 2010 Dec;17(12):1438-45
references.pmid: 21057524
references.citation: PLoS Genet. 2011 Mar;7(3):e1002024
references.pmid: 21437267
references.citation: Am J Epidemiol. 2012 Mar 1;175(5):414-22
references.pmid: 22302075