• Open Access

Base excision repair activities required for yeast to attain a full chronological life span

Authors

  • Morag J. Maclean,

    1. Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK
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    • *

      Current address: Département de Biologie Cellulaire, Universite de Génève, Sciences III, 30, Quai Ernest-Ansermet, CH – 1211 Génève 4, Switzerland.

  • Randi Aamodt,

    1. Centre of Molecular Biology and Neuroscience and Institute of Medical Microbiology, University of Oslo, The National Hospital, N-0027 Oslo, Norway
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  • Nicholas Harris,

    1. Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK
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  • Ingrun Alseth,

    1. Centre of Molecular Biology and Neuroscience and Institute of Medical Microbiology, University of Oslo, The National Hospital, N-0027 Oslo, Norway
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  • Erling Seeberg,

    1. Centre of Molecular Biology and Neuroscience and Institute of Medical Microbiology, University of Oslo, The National Hospital, N-0027 Oslo, Norway
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  • Magnar Bjørås,

    1. Centre of Molecular Biology and Neuroscience and Institute of Medical Microbiology, University of Oslo, The National Hospital, N-0027 Oslo, Norway
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  • Peter W. Piper

    Corresponding author
    1. Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK
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Dr Peter W. Piper, Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK. Tel.: +44 207679 2212; fax: +44 207679 7193; e-mail: piper@bsm.bioc.ucl.ac.uk

Summary

The chronological life span of yeast, the survival of stationary (G0) cells over time, provides a model for investigating certain of the factors that may influence the aging of non-dividing cells and tissues in higher organisms. This study measured the effects of defined defects in the base excision repair (BER) system for DNA repair on this life span. Stationary yeast survives longer when it is pregrown on respiratory, as compared to fermentative (glucose), media. It is also less susceptible to viability loss as the result of defects in DNA glycosylase/AP lyases (Ogg1p, Ntg1p, Ntg2p), apurinic/apyrimidinic (AP) endonucleases (Apn1p, Apn2p) and monofunctional DNA glycosylase (Mag1p). Whereas single BER glycosylase/AP lyase defects exerted little influence over such optimized G0 survival, this survival was severely shortened with the loss of two or more such enzymes. Equally, the apn1Δ and apn2Δ single gene deletes survived as well as the wild type, whereas a apn1Δapn2Δ double mutant totally lacking in any AP endonuclease activity survived poorly. Both this shortened G0 survival and the enhanced mutagenicity of apn1Δapn2Δ cells were however rescued by the overexpression of either Apn1p or Apn2p. The results highlight the vital importance of BER in the prevention of mutation accumulation and the attainment of the full yeast chronological life span. They also reveal an appreciable overlap in the G0 maintenance functions of the different BER DNA glycosylases and AP endonucleases.

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