Polyphosphate is a key factor for cell survival after DNA damage in eukaryotic cells |
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Institution: | 1. Research Group on Nutrition: Molecular, Pathophysiological and Social Issues, University of Cadiz, Spain;2. Research Unit, ‘Puerta del Mar’ University Hospital, Spain;3. San Carlos Hospital, Cadiz, Spain;4. Department of Biomedicine, Biotechnology and Public Health, University of Cadiz., Spain;1. Department of Basic Sciences, New York University College of Dentistry, 345 East 24th Street, 10010 New York, NY, USA;2. Department of Cancer Biology and Pharmacology, 1 Illini Drive, 61605 Peoria, IL, USA |
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Abstract: | 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. |
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Keywords: | Mammalian cells Human dermal fibroblasts Polyphosphate DNA damage Repair |
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