Bollé, Sarune;
Koc, Elisa;
Saiardi, Adolfo;
Juhran, Lisa;
Walla, Eva;
Fleig, Ursula;
Alcázar-Román, Abel;
(2025)
Inorganic Polyphosphate Modulates Chromosome Transmission Fidelity in the Fission Yeast Schizosaccharomyces pombe.
Biomolecules
, 15
(9)
, Article 1331. 10.3390/biom15091331.
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Inorganic Polyphosphate Modulates Chromosome Transmission Fidelity in the Fission Yeast <i>Schizosaccharomyces pombe&l.pdf - Published Version Download (4MB) | Preview |
Abstract
Chromosome transmission fidelity is vital for organism fitness. Yet, extrinsic and intrinsic changes can affect this process, leading to aneuploidy, the loss/gain of chromosomes, which is a hallmark of cancer. Here, using a haploid fission yeast Schizosaccharomyces pombe strain with a segmental aneuploidy, we assayed genome stability under different temperatures and altered gene dosage. We find that S. pombe genome stability is temperature-dependent and is unexpectedly modulated by intracellular levels of inorganic polyphosphate polymers (polyP). The vtc4+ gene, encoding a subunit of the polyP-generating VTC complex, is present twice due to the segmental aneuploidy resulting in a gene-dosage-coupled increase in polyP. Using strains with different amounts of polyP, we find a direct negative correlation between polyP and chromosome segregation fidelity. PolyP modulates the function of the conserved CCAN kinetochore subcomplex, as the abnormal growth phenotype caused by the mutant CCAN protein Fta2-291 was rescued in the absence of polyP, while extra polyP had the opposite effect. Importantly, this appears to occur in part by modulation of the nucleolin Gar2. Gar2 is the functional homolog of the Saccharomyces cerevisiae Nsr1 protein, whose function is modulated by posttranslational polyP-mediated polyphosphorylation. Thus, polyP modulates genome stability, linking cellular metabolism to chromosome transmission fidelity.
| Type: | Article |
|---|---|
| Title: | Inorganic Polyphosphate Modulates Chromosome Transmission Fidelity in the Fission Yeast Schizosaccharomyces pombe |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/biom15091331 |
| Publisher version: | https://doi.org/10.3390/biom15091331 |
| Language: | English |
| Additional information: | Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/ licenses/by/4.0/). |
| Keywords: | CCAN complex, Schizosaccharomyces pombe, aneuploidy, gene dosage, genome stability, inorganic polyphosphate, kinetochore, polyP, yeast, Schizosaccharomyces, Polyphosphates, Schizosaccharomyces pombe Proteins, Chromosomes, Fungal, Chromosome Segregation, Genomic Instability, Aneuploidy |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10215059 |
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