Polyphosphate is involved in cell cycle progression and genomic stability in Saccharomyces cerevisiae

Abstract

Polyphosphate (polyP) is a linear chain of up to hundreds of inorganic phosphate residues that is necessary for many physiological functions in all living organisms. In some bacteria, polyP supplies material to molecules such as DNA, thus playing an important role in biosynthetic processes in prokaryotes. In the present study, we set out to gain further insight into the role of polyP in eukaryotic cells. We observed that polyP amounts are cyclically regulated in Saccharomyces cerevisiae, and those mutants that cannot synthesise (vtc4Δ) or hydrolyse polyP (ppn1Δ, ppx1Δ) present impaired cell cycle progression. Further analysis revealed that polyP mutants show delayed nucleotide production and increased genomic instability. Based on these findings, we concluded that polyP not only maintains intracellular phosphate concentrations in response to fluctuations in extracellular phosphate levels, but also muffles internal cyclic phosphate fluctuations, such as those produced by the sudden demand of phosphate to synthetize deoxynucleotides just before and during DNA duplication. We propose that the presence of polyP in eukaryotic cells is required for the timely and accurate duplication of DNA.

Polyphosphate granule biogenesis is temporally and functionally tied to cell cycle exit during starvation in Pseudomonas aeruginosa

“…PolyP as a phosphate sink may therefore be critical for cellular equilibrium. A role for polyP in nucleotide homeostasis has been recently proposed in yeast, where oscillation in the concentration of polyP measured biochemically was observed to correlate with cell cycle progression, in the absence of starvation (32). One of the functions of (p)ppGpp during starvation in B. subtilis is suppression of GTP biosynthesis, which unchecked leads to cell death (33).…”

“…Most eukaryotes lack (p)ppGpp, but a number of recent studies in eukaryotes suggest that polyP may be important in cell cycle regulation more broadly. In Dictyostelium discoideum, polyP is required for cytokinesis as well as spore germination; in Saccharomyces cerevisiae, polyP concentrations oscillate in a cell cycle-dependent manner and influence the rate of progression from G1 to S phase, affecting genomic stability; and in a mammalian cancer cell line, polyP was found to stimulate mTor kinase and promote cell proliferation (32,(52)(53)(54). It is thus tempting to speculate that polyP may be a universal mediator between metabolic cues and the cell cycle.…”

Vtc5, a Novel Subunit of the Vacuolar Transporter Chaperone Complex, Regulates Polyphosphate Synthesis and Phosphate Homeostasis in Yeast

“…PolyP also serves as a P i source to facilitate rapid DNA synthesis in S-phase, which transiently drains more P i than the cells can take up via their transporters (48). During S-phase, cytosolic P i concentrations are held constant, although the polyP reserves are consumed, which suggests that net polyP synthesis should be down-regulated.…”

Ppn2, a novel Zn2+-dependent polyphosphatase in the acidocalcisome-like yeast vacuole

“…PolyP is used as a phosphate reserve that can sustain growth under phosphate scarcity or under acute high metabolic demand, as for example for dNTP synthesis during the S phase of the cell cycle (Bru et al, 2016). Synthesis and degradation of polyP are required to buffer cytosolic P i concentration, and this is essential for cells in order to adapt to changing phosphate availability in the environment.…”