Molecular Biology Reports

, Volume 39, Issue 4, pp 3573–3583 | Cite as

Compromised cellular responses to DNA damage accelerate chronological aging by incurring cell wall fragility in Saccharomyces cerevisiae

  • Shanshan Yu
  • Xian-en Zhang
  • Guanjun Chen
  • Weifeng Liu


Elevated levels of reactive oxygen species (ROS) can attack almost all cell components including genomic DNA to induce many types of DNA damage. In this study, we used Saccharomyces cerevisiae with various mutations in a biological network supposed to prevent deleterious effects of endogenous ROS to test the effect of such a network on yeast chronological aging. Our results showed that cells with defects in cellular antioxidation, DNA repair and DNA damage checkpoints displayed a mutation rate higher than that of wild-type strain. Moreover, the chronological life span of most mutants as determined by colony formation was found to be shorter than that of wild-type cells, especially for the mutants defective in DNA replication and DNA damage checkpoints, although the observed cell number was almost the same for wild-type and mutant strains. The mutants were finally found to be more sensitive to SDS and lysing enzyme treatment, and that the degree of sensitivity was correlated with their chronological life span.


Chronological aging DNA damage repair Checkpoint Genome stability Antioxidation 


  1. 1.
    Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408(6809):239–247. doi:10.1038/35041687 PubMedCrossRefGoogle Scholar
  2. 2.
    Costa V, Moradas-Ferreira P (2001) Oxidative stress and signal transduction in Saccharomyces cerevisiae: insights into ageing, apoptosis and diseases. Mol Aspects Med 22(4–5):217–246PubMedCrossRefGoogle Scholar
  3. 3.
    Klaunig JE, Kamendulis LM (2004) The role of oxidative stress in carcinogenesis. Annu Rev Pharmacol Toxicol 44:239–267. doi:10.1146/annurev.pharmtox.44.101802.121851 PubMedCrossRefGoogle Scholar
  4. 4.
    Park SG, Cha MK, Jeong W, Kim IH (2000) Distinct physiological functions of thiol peroxidase isoenzymes in Saccharomyces cerevisiae. J Biol Chem 275(8):5723–5732PubMedCrossRefGoogle Scholar
  5. 5.
    Biteau B, Labarre J, Toledano MB (2003) ATP-dependent reduction of cysteine-sulphinic acid by S. cerevisiae sulphiredoxin. Nature 425(6961):980–984. doi:10.1038/nature02075 PubMedCrossRefGoogle Scholar
  6. 6.
    Huang ME, Rio AG, Nicolas A, Kolodner RD (2003) A genomewide screen in Saccharomyces cerevisiae for genes that suppress the accumulation of mutations. Proc Natl Acad Sci USA 100(20):11529–11534. doi:10.1073/pnas.2035018100 PubMedCrossRefGoogle Scholar
  7. 7.
    Doetsch PW, Morey NJ, Swanson RL, Jinks-Robertson S (2001) Yeast base excision repair: interconnections and networks. Prog Nucleic Acid Res Mol Biol 68:29–39PubMedCrossRefGoogle Scholar
  8. 8.
    Rouse J, Jackson SP (2002) Interfaces between the detection, signaling, and repair of DNA damage. Science 297(5581):547–551. doi:10.1126/science.1074740 PubMedCrossRefGoogle Scholar
  9. 9.
    Kolodner RD, Putnam CD, Myung K (2002) Maintenance of genome stability in Saccharomyces cerevisiae. Science 297(5581):552–557. doi:10.1126/science.1075277 PubMedCrossRefGoogle Scholar
  10. 10.
    Huang ME, Kolodner RD (2005) A biological network in Saccharomyces cerevisiae prevents the deleterious effects of endogenous oxidative DNA damage. Mol Cell 17(5):709–720. doi:10.1016/j.molcel.2005.02.008 PubMedCrossRefGoogle Scholar
  11. 11.
    MacLean M, Harris N, Piper PW (2001) Chronological lifespan of stationary phase yeast cells; a model for investigating the factors that might influence the ageing of postmitotic tissues in higher organisms. Yeast 18(6):499–509. doi:10.1002/yea.701 PubMedCrossRefGoogle Scholar
  12. 12.
    Longo VD, Ellerby LM, Bredesen DE, Valentine JS, Gralla EB (1997) Human Bcl-2 reverses survival defects in yeast lacking superoxide dismutase and delays death of wild-type yeast. J Cell Biol 137(7):1581–1588PubMedCrossRefGoogle Scholar
  13. 13.
    Madeo F, Frohlich E, Ligr M, Grey M, Sigrist SJ, Wolf DH, Frohlich KU (1999) Oxygen stress: a regulator of apoptosis in yeast. J Cell Biol 145(4):757–767PubMedCrossRefGoogle Scholar
  14. 14.
    Herker E, Jungwirth H, Lehmann KA, Maldener C, Frohlich KU, Wissing S, Buttner S, Fehr M, Sigrist S, Madeo F (2004) Chronological aging leads to apoptosis in yeast. J Cell Biol 164(4):501–507. doi:10.1083/jcb.200310014 PubMedCrossRefGoogle Scholar
  15. 15.
    Kirkwood TB, Austad SN (2000) Why do we age? Nature 408(6809):233–238. doi:10.1038/35041682 PubMedCrossRefGoogle Scholar
  16. 16.
    Barros MH, Bandy B, Tahara EB, Kowaltowski AJ (2004) Higher respiratory activity decreases mitochondrial reactive oxygen release and increases life span in Saccharomyces cerevisiae. J Biol Chem 279(48):49883–49888. doi:10.1074/jbc.M408918200 PubMedCrossRefGoogle Scholar
  17. 17.
    Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308(5730):1909–1911. doi:10.1126/science.1106653 PubMedCrossRefGoogle Scholar
  18. 18.
    Koc A, Gasch AP, Rutherford JC, Kim HY, Gladyshev VN (2004) Methionine sulfoxide reductase regulation of yeast lifespan reveals reactive oxygen species-dependent and -independent components of aging. Proc Natl Acad Sci USA 101(21):7999–8004. doi:10.1073/pnas.0307929101 PubMedCrossRefGoogle Scholar
  19. 19.
    Burhans WC, Weinberger M (2007) DNA replication stress, genome instability and aging. Nucleic Acids Res 35(22):7545–7556. doi:10.1093/nar/gkm1059 PubMedCrossRefGoogle Scholar
  20. 20.
    Reverter-Branchat G, Cabiscol E, Tamarit J, Sorolla MA, Angeles de la Torre M, Ros J (2007) Chronological and replicative life-span extension in Saccharomyces cerevisiae by increased dosage of alcohol dehydrogenase 1. Microbiology 153(Pt 11):3667–3676. doi:10.1099/mic.0.2007/009340-0 PubMedCrossRefGoogle Scholar
  21. 21.
    Myung K, Datta A, Kolodner RD (2001) Suppression of spontaneous chromosomal rearrangements by S phase checkpoint functions in Saccharomyces cerevisiae. Cell 104(3):397–408PubMedCrossRefGoogle Scholar
  22. 22.
    Guldener U, Heck S, Fielder T, Beinhauer J, Hegemann JH (1996) A new efficient gene disruption cassette for repeated use in budding yeast. Nucleic Acids Res 24(13):2519–2524PubMedCrossRefGoogle Scholar
  23. 23.
    Tishkoff DX, Filosi N, Gaida GM, Kolodner RD (1997) A novel mutation avoidance mechanism dependent on S. cerevisiae RAD27 is distinct from DNA mismatch repair. Cell 88(2):253–263PubMedCrossRefGoogle Scholar
  24. 24.
    Salmon TB, Evert BA, Song B, Doetsch PW (2004) Biological consequences of oxidative stress-induced DNA damage in Saccharomyces cerevisiae. Nucleic Acids Res 32(12):3712–3723. doi:10.1093/nar/gkh696 PubMedCrossRefGoogle Scholar
  25. 25.
    Wysocki R, Kron SJ (2004) Yeast cell death during DNA damage arrest is independent of caspase or reactive oxygen species. J Cell Biol 166(3):311–316. doi:10.1083/jcb.200405016 PubMedCrossRefGoogle Scholar
  26. 26.
    Enserink JM, Smolka MB, Zhou H, Kolodner RD (2006) Checkpoint proteins control morphogenetic events during DNA replication stress in Saccharomyces cerevisiae. J Cell Biol 175(5):729–741. doi:10.1083/jcb.200605080 PubMedCrossRefGoogle Scholar
  27. 27.
    Liberi G, Maffioletti G, Lucca C, Chiolo I, Baryshnikova A, Cotta-Ramusino C, Lopes M, Pellicioli A, Haber JE, Foiani M (2005) Rad51-dependent DNA structures accumulate at damaged replication forks in sgs1 mutants defective in the yeast ortholog of BLM RecQ helicase. Genes Dev 19(3):339–350. doi:10.1101/gad.322605 PubMedCrossRefGoogle Scholar
  28. 28.
    Qi H, Li TK, Kuo D, Nur EKA, Liu LF (2003) Inactivation of Cdc13p triggers MEC1-dependent apoptotic signals in yeast. J Biol Chem 278(17):15136–15141. doi:10.1074/jbc.M212808200 PubMedCrossRefGoogle Scholar
  29. 29.
    Lans H, Hoeijmakers JH (2006) Cell biology: ageing nucleus gets out of shape. Nature 440(7080):32–34. doi:10.1038/440032a PubMedCrossRefGoogle Scholar
  30. 30.
    Qin H, Lu M, Goldfarb DS (2008) Genomic instability is associated with natural life span variation in Saccharomyces cerevisiae. PLoS One 3(7):e2670. doi:10.1371/journal.pone.0002670 PubMedCrossRefGoogle Scholar
  31. 31.
    Evert BA, Salmon TB, Song B, Jingjing L, Siede W, Doetsch PW (2004) Spontaneous DNA damage in Saccharomyces cerevisiae elicits phenotypic properties similar to cancer cells. J Biol Chem 279(21):22585–22594. doi:10.1074/jbc.M400468200 PubMedCrossRefGoogle Scholar
  32. 32.
    Heinisch JJ, Lorberg A, Schmitz HP, Jacoby JJ (1999) The protein kinase C-mediated MAP kinase pathway involved in the maintenance of cellular integrity in Saccharomyces cerevisiae. Mol Microbiol 32(4):671–680PubMedCrossRefGoogle Scholar
  33. 33.
    Stewart MS, Krause SA, McGhie J, Gray JV (2007) Mpt5p, a stress tolerance- and lifespan-promoting PUF protein in Saccharomyces cerevisiae, acts upstream of the cell wall integrity pathway. Eukaryot Cell 6(2):262–270. doi:10.1128/EC.00188-06 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Shanshan Yu
    • 1
  • Xian-en Zhang
    • 2
  • Guanjun Chen
    • 1
  • Weifeng Liu
    • 1
  1. 1.The State Key Laboratory of Microbial Technology, School of Life ScienceShandong UniversityJinanPeople’s Republic of China
  2. 2.Wuhan Institute of VirologyChinese Academy of SciencesWuhanPeople’s Republic of China

Personalised recommendations