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Nitrogen availability and TOR signalling are important for preventing catastrophic mitosis in fission yeast

Zemlianski, V.; Maresova, A.; Princova, J.; Holic, R.; Häsler, R.; Ramos del Rio, M. J.; Lhoste, L.; Zarechyntsava, M.; Prevorovsky, M.

2023-12-27 cell biology
10.1101/2023.12.25.573293 bioRxiv
Show abstract

Mitosis is a critical stage in the cell cycle, controlled by a vast network of regulators responding to multiple internal and external factors. The fission yeast Schizosaccharomyces pombe may demonstrate catastrophic mitotic phenotypes due to mutations or drug treatments. One of the factors provoking catastrophic mitosis is a disturbed lipid metabolism, resulting from e.g. mutations in acetyl-CoA/biotin carboxylase (cut6), in fatty acid synthase (fas2/lsd1), or in the transcriptional regulator of lipid metabolism (cbf11) genes, as well as treatment with inhibitors of fatty acid synthesis. It was previously shown that mitotic fidelity in lipid metabolism mutants can be partially rescued by ammonium chloride. In this study we demonstrate that mitotic fidelity can be improved by multiple good nitrogen sources. Moreover, this rescue is not limited to lipid metabolism disturbances but also applies to a number of unrelated mitotic mutants. Interestingly, the rescue is not achieved by restoring the lipid metabolism state, but rather indirectly. We found that the TOR regulatory network plays a major role in mediating such rescue, highlighting a novel role for TOR in mitotic fidelity.

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