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

Area of Science:

• Molecular Biology
• Biochemistry
• Cell Biology

Background:

• Cells need increased deoxyribonucleotide triphosphates (dNTPs) for DNA repair following damage.
• Polyphosphate (polyP) is a conserved polymer of inorganic phosphate (Pi) with diverse cellular roles, including Pi storage.

Purpose of the Study:

• To investigate the role of polyphosphate (polyP) in cellular DNA repair mechanisms.
• To determine if polyP serves as a source of inorganic phosphate (Pi) for dNTP synthesis during DNA repair.

Main Methods:

• Utilized mutant yeast strains lacking polyP and wild-type strains with elevated polyP.
• Assessed dNTP levels and DNA damage survival rates in yeast and human cell lines (HEK293, HDFa) with altered polyP levels.

Main Results:

• Yeast cells deficient in polyP showed reduced dNTP production and compromised survival after DNA damage.
• Increased polyP levels enhanced yeast resistance to DNA damage.
• Reduced polyP in human cells increased sensitivity to DNA damage, indicating evolutionary conservation.

Conclusions:

• Polyphosphate (polyP) acts as a crucial source of inorganic phosphate (Pi) to sustain dNTP pools for DNA repair.
• The protective function of polyP against DNA damage is evolutionarily conserved from yeast to human cells.
• PolyP represents a potential therapeutic target for cancer treatment and prevention strategies.