Format

Send to

Choose Destination
DNA Repair (Amst). 2017 Sep;57:171-178. doi: 10.1016/j.dnarep.2017.08.001. Epub 2017 Aug 8.

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

Author information

1
Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona, Spain.
2
Institut de Recerca Biomèdica de Lleida (IRBLleida), Departament de Ciències Mèdiques Bàsiques, Facultat de Medicina, Universitat de Lleida, Lleida, Spain.
3
Research Group on Neuromuscular and Mitochondrial Disorders, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain; Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.
4
Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona, Spain. Electronic address: jjimenez@uic.es.
5
Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona, Spain. Electronic address: jclotet@uic.cat.

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.

KEYWORDS:

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

PMID:
28822913
DOI:
10.1016/j.dnarep.2017.08.001
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center