Polyphosphate is a key factor for cell survival after DNA damage in eukaryotic cells

Samuel Bru, Bàrbara Samper-Martín, Eva Quandt, Sara Hernández-Ortega, Joan M. Martínez-Laínez, Eloi Garí, Marta Rafel, Javier Torres-Torronteras, Ramón Martí, Mariana P.C. Ribeiro, Javier Jiménez, Josep Clotet

    Research output: Contribution to journalArticleResearchpeer-review

    11 Citations (Scopus)

    Abstract

    © 2017 Elsevier B.V. Cells require extra amounts of dNTPs to repair DNA after damage. Polyphosphate (polyP) is an evolutionary conserved linear polymer of up to several hundred inorganic phosphate (Pi) residues that is involved in many functions, including Pi storage. In the present article, we report on findings demonstrating that polyP functions as a source of Pi when required to sustain the dNTP increment essential for DNA repair after damage. We show that mutant yeast cells without polyP produce less dNTPs upon DNA damage and that their survival is compromised. In contrast, when polyP levels are ectopically increased, yeast cells become more resistant to DNA damage. More importantly, we show that when polyP is reduced in HEK293 mammalian cell line cells and in human dermal primary fibroblasts (HDFa), these cells become more sensitive to DNA damage, suggesting that the protective role of polyP against DNA damage is evolutionary conserved. In conclusion, we present polyP as a molecule involved in resistance to DNA damage and suggest that polyP may be a putative target for new approaches in cancer treatment or prevention.
    Original languageEnglish
    Pages (from-to)171-178
    JournalDNA Repair
    Volume57
    DOIs
    Publication statusPublished - 1 Sep 2017

    Keywords

    • DNA damage
    • Human dermal fibroblasts
    • Mammalian cells
    • Polyphosphate
    • Repair
    • Saccharomyces

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