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Inactivation of RAD52 and HDF1 DNA repair genes leads to premature chronological aging and cellular instability

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Abstract

The present study aims to investigate the role of radiation sensitive 52 (RAD52) and high-affinity DNA binding factor 1 (HDF1) DNA repair genes on the life span of budding yeasts during chronological aging. Wild type (wt) and rad52, hdf1, and rad52 hdf1 mutant Saccharomyces cerevisiae strains were used. Chronological aging and survival assays were studied by clonogenic assay and drop test. DNA damage was analyzed by electrophoresis after phenol extraction. Mutant analysis, colony forming units and the index of respiratory competence were studied by growing on dextrose and glycerol plates as a carbon source. Rad52 and rad52 hdf1 mutants showed a gradual decrease in surviving fraction in relation to wt and hdf1 mutant during aging. Genomic DNA was spontaneously more degraded during aging, mainly in rad52 mutants. This strain showed an increased percentage of revertant colonies. Moreover, all mutants showed a decrease in the index of respiratory competence during aging. The inactivation of RAD52 leads to premature chronological aging with an increase in DNA degradation and mutation frequency. In addition, RAD52 and HDF1 contribute to maintain the metabolic state, in a different way, during chronological aging. The results obtained could have important implications in the chronobiology of aging.

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Acknowledgements

We express our gratitude to Dr Anna A Friedl (Department of Radiation Oncology, Ludwig-Maximilians-Universität München, Munich, Germany) for kindly providing the yeast strains. We also thank Ms L Gil Carmona (Universidad de Málaga, Spain) for her technical assistance.

This study was supported by the ‘Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI); Junta de Andalucía’, [CTS-181].

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Authors and Affiliations

  1. Facultad de Medicina, Departamento de Radiología y Medicina Física, Universidad de Málaga, Málaga, España

    Silvia Mercado-Sáenz, Beatriz López-Díaz, Francisco Sendra-Portero, Manuel Martínez-Morillo & Miguel J Ruiz-Gómez

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  1. Silvia Mercado-Sáenz
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  2. Beatriz López-Díaz
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  3. Francisco Sendra-Portero
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  4. Manuel Martínez-Morillo
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  5. Miguel J Ruiz-Gómez
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Correspondence to Miguel J Ruiz-Gómez.

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† In memoriam.

[Mercado-Sáenz S, López-Díaz B, Sendra-Portero F, Martínez-Morillo M and Ruiz-Gómez MJ 2017 Inactivation of RAD52 and HDF1 DNA repair genes leads to premature chronological aging and cellular instability. J. Biosci.]

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Mercado-Sáenz, S., López-Díaz, B., Sendra-Portero, F. et al. Inactivation of RAD52 and HDF1 DNA repair genes leads to premature chronological aging and cellular instability. J Biosci 42, 219–230 (2017). https://doi.org/10.1007/s12038-017-9684-7

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  • DOI: https://doi.org/10.1007/s12038-017-9684-7

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