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

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. We would like to thank all the members of our group (E. Bállega, O. Mirallas, M. Ribeiro, A. Sánchez, B. Semper, and R. Carballar) for day-to-day talks, and Marta Pérez for technical assistance. The yeast ppn1Δ, ppn2Δ, ppx1Δ strain is a kind gift from A Mayer (Université de Lausanne). This work was supported by funding from the Spanish Government, with a MINECO grant (Ref: BFU 2013-44189-P) awarded to J. Clotet and a MICINN grant (Ref: BFU 2013-42895-P) awarded to E. Garí. J.M.M. was the recipient of a post-graduate Junior Faculty Fellowship from the UIC and l’Obra Social la Caixa.