Bru Samuel, Martínez-Laínez Joan Marc, Hernández-Ortega Sara, Quandt Eva, Torres-Torronteras Javier, Martí Ramón, Canadell David, Ariño Joaquin, Sharma Sushma, Jiménez Javier, Clotet Josep
Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona, Spain.
Research Group on Neuromuscular and Mitochondrial Disorders, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain.
Mol Microbiol. 2016 Aug;101(3):367-80. doi: 10.1111/mmi.13396. Epub 2016 May 3.
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.
多聚磷酸盐(polyP)是由多达数百个无机磷酸残基组成的线性链,对所有生物体的许多生理功能都是必需的。在一些细菌中,多聚磷酸盐为DNA等分子提供物质,因此在原核生物的生物合成过程中发挥重要作用。在本研究中,我们着手进一步深入了解多聚磷酸盐在真核细胞中的作用。我们观察到,酿酒酵母中的多聚磷酸盐含量受到周期性调节,那些不能合成(vtc4Δ)或水解多聚磷酸盐(ppn1Δ、ppx1Δ)的突变体,其细胞周期进程受损。进一步分析表明,多聚磷酸盐突变体显示出核苷酸生成延迟和基因组不稳定性增加。基于这些发现,我们得出结论,多聚磷酸盐不仅能响应细胞外磷酸盐水平的波动来维持细胞内磷酸盐浓度,还能抑制内部循环磷酸盐的波动,比如在DNA复制之前和期间因突然需要磷酸盐来合成脱氧核苷酸而产生的波动。我们提出,真核细胞中多聚磷酸盐的存在是DNA及时、准确复制所必需的。