title: Increased genome instability is not accompanied by sensitivity to DNA damaging agents in aged yeast cells.
abstract: The budding yeast Saccharomyces cerevisiae divides asymmetrically, producing a new daughter cell from the original mother cell. While daughter cells are born with a full lifespan, a mother cell ages with each cell division and can only generate on average 25 daughter cells before dying. Aged yeast cells exhibit genomic instability, which is also a hallmark of human aging. However, it is unclear how this genomic instability contributes to aging. To shed light on this issue, we investigated endogenous DNA damage in S. cerevisiae during replicative aging and tested for age-dependent sensitivity to exogenous DNA damaging agents. Using live-cell imaging in a microfluidic device, we show that aging yeast cells display an increase in spontaneous Rad52 foci, a marker of endogenous DNA damage. Strikingly, this elevated DNA damage is not accompanied by increased sensitivity of aged yeast cells to genotoxic agents nor by global changes in the proteome or transcriptome that would indicate a specific "DNA damage signature". These results indicate that DNA repair proficiency is not compromised in aged yeast cells, suggesting that yeast replicative aging and age-associated genomic instability is likely not a consequence of an inability to repair DNA damage.
authors.affiliation: European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands.
authors.forename: Daniele
authors.initials: D
authors.lastname: Novarina
authors.affiliation: European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands.
authors.forename: Sara N
authors.initials: SN
authors.lastname: Mavrova
authors.affiliation: European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands.
authors.forename: Georges E
authors.initials: GE
authors.lastname: Janssens
authors.affiliation: European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands.
authors.forename: Irina L
authors.initials: IL
authors.lastname: Rempel
authors.affiliation: European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands.
authors.forename: Liesbeth M
authors.initials: LM
authors.lastname: Veenhoff
authors.affiliation: European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands. Electronic address: m.chang@umcg.nl.
authors.forename: Michael
authors.initials: M
authors.lastname: Chang
mesh_terms: D000375:Aging; D002455:Cell Division; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004271:DNA, Fungal / Q000378:metabolism; D042822:Genomic Instability; D051721:Rad52 DNA Repair and Recombination Protein; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D004271:DNA, Fungal; C497197:RAD52 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; D029701:Saccharomyces cerevisiae Proteins
keywords: DNA damage sensitivity; Genome stability; Rad52; Yeast aging