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

Bru, Samuel; Samper-Martín, Bàrbara; Quandt, Eva; Hernández-Ortega, Sara; Martínez-Láinez, Joan Marc; Garí, Eloi; Rafel, Marta; Torres‐Torronteras, Javier; Martí, Ramón; Ribeiro, Mariana P.C.; Jiménez, Javier; Clotet, Josep

doi:10.1016/j.dnarep.2017.08.001

Cited by 27 publications

(32 citation statements)

References 69 publications

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“…PolyP localization in eukaryotic cells has been reported in nuclei, mitochondria, and cytosol [36][37][38][39]. However, there are no reports citing the localization of polyP in ER.…”

Section: Polyp Colocalizes With Cypb In Er Of Nondifferentiated Saos-mentioning

confidence: 99%

Inorganic polyphosphate controls cyclophilin B‐mediated collagen folding in osteoblast‐like cells

Khong

Solesio

et al. 2020

The FEBS Journal

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Evidence is emerging that inorganic polyphosphate (polyP) is a fundamental molecule involved in a wide range of biological processes. In higher eukaryotes, polyP is abundant in osteoblasts but questions remain as to its functions. Here, we find that polyP is particularly enriched in endoplasmic reticulum (ER) where it colocalizes with cyclophilin B (CypB) using osteoblastic SaOS-2 model cell line. PolyP binds directly and specifically to CypB, inhibiting its peptidyl-prolyl cis-trans isomerase activity which is critical for collagen folding. PolyP sequestration by spermine and ERspecific polyP reduction by polyphosphatase expression in cells reduced collagen misfolding and confirmed that endogenous polyP acts as a molecular control of CypB-mediated collagen folding. We propose that polyP is a previously unrecognized critical regulator of protein homeostasis in ER.

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“…PolyP localization in eukaryotic cells has been reported in nuclei, mitochondria, and cytosol [36][37][38][39]. However, there are no reports citing the localization of polyP in ER.…”

Section: Polyp Colocalizes With Cypb In Er Of Nondifferentiated Saos-mentioning

confidence: 99%

Inorganic polyphosphate controls cyclophilin B‐mediated collagen folding in osteoblast‐like cells

Khong

Solesio

et al. 2020

The FEBS Journal

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“…Chabes et al reported that DNA damage induced by 4-nitroquinoline-N-oxide (4-NQO) led to a 6 to 8 fold increase of dNTPs levels, which dramatically improved survival following DNA damage in in yeast cells [ 5 ]. However, for mutant yeast cells which fail to produce sufficient dNTPs upon DNA damage, their survival is compromised [ 6 ]. Compared with yeast, mammalian cells possess different mechanisms to regulate dNTPs perturbation caused by DNA damage [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Profiling of ribonucleotides and deoxyribonucleotides pools in response to DNA damage and repair induced by methyl methanesulfonate in cancer and normal cells

Guo

Wang

et al. 2017

Oncotarget

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The absolute and relative pool sizes of deoxyribonucleotides (dRNs) are essential in DNA replication fidelity, DNA damage and repair. We found in this study that although DNA damage induced by methyl methanesulfonate (MMS) seemed similar in cancer (HepG2) and normal (LO2) cells, more extensive alterations in ribonucleotides (RNs) and dRNs pools occurred in HepG2 cells indicating that HepG2 cells were more vigilant to DNA damage. After 10 h repair, RNs pools were still severely perturbed in LO2 cells. Compared to LO2 cells, deoxyribonucleotide triphosphates (dNTPs) pools in HepG2 cells elevated by more folds which could facilitate more efficient DNA repair and improve survival probability following DNA damage, although this should definitely lead to higher mutation rates. DNA repair was more efficient in HepG2 cells at S phase and it partly came to an end while DNA repair was still uncompleted in LO2 cells outside S phase. In conclusion, our results demonstrated that HepG2 and LO2 cells presented many differences in nucleotide metabolism, cell cycle checkpoints and DNA repair pathways in response to DNA damage, which could be potential targets for cancer treatment.

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“…The exact role of the PASK domains and N -polyphosphorylation is not understood although it is known that polyphosphates in general (not necessarily N -polyphosphates) participate in a variety of processes ranging from regulating core metabolism to structural roles [370]. It was recently suggested that polyphosphates are one of the key factors required for cell survival after DNA damage in eukaryotic cells [373]. It is therefore intriguing to speculate if N -polyphosphorylation also participates in these processes.…”

Section: Natural Products Containing a P–n Bond (Phosphoramidates)mentioning

confidence: 99%

Natural Products Containing ‘Rare’ Organophosphorus Functional Groups

2019

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Phosphorous-containing molecules are essential constituents of all living cells. While the phosphate functional group is very common in small molecule natural products, nucleic acids, and as chemical modification in protein and peptides, phosphorous can form P–N (phosphoramidate), P–S (phosphorothioate), and P–C (e.g., phosphonate and phosphinate) linkages. While rare, these moieties play critical roles in many processes and in all forms of life. In this review we thoroughly categorize P–N, P–S, and P–C natural organophosphorus compounds. Information on biological source, biological activity, and biosynthesis is included, if known. This review also summarizes the role of phosphorylation on unusual amino acids in proteins (N- and S-phosphorylation) and reviews the natural phosphorothioate (P–S) and phosphoramidate (P–N) modifications of DNA and nucleotides with an emphasis on their role in the metabolism of the cell. We challenge the commonly held notion that nonphosphate organophosphorus functional groups are an oddity of biochemistry, with no central role in the metabolism of the cell. We postulate that the extent of utilization of some phosphorus groups by life, especially those containing P–N bonds, is likely severely underestimated and has been largely overlooked, mainly due to the technological limitations in their detection and analysis.

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

Cited by 27 publications

References 69 publications

Inorganic polyphosphate controls cyclophilin B‐mediated collagen folding in osteoblast‐like cells

Inorganic polyphosphate controls cyclophilin B‐mediated collagen folding in osteoblast‐like cells

Profiling of ribonucleotides and deoxyribonucleotides pools in response to DNA damage and repair induced by methyl methanesulfonate in cancer and normal cells

Natural Products Containing ‘Rare’ Organophosphorus Functional Groups

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