Escape from mitotic catastrophe by actin-dependent nuclear displacement in fission yeast

Yukawa, Masashi; Teratani, Yasuhiro; Toda, Takashi

doi:10.1016/j.isci.2020.102031

Cited by 8 publications

(4 citation statements)

References 60 publications

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“…These include: ‘cut’ - c ell u ntimely torn, a form of mitotic catastrophe where cytokinesis takes place before nuclear division has been properly resolved, and the mother nucleus gets transected by and trapped in the forming septum (Fig. 1 A) [7][8]; ‘lsd’ - large and s mall d aughters, a segregation error where the resulting daughter nuclei are of unequal sizes [9]; and nucleus displacement, which is similar to ‘cut’, but the forming septum misses the nucleus, resulting in one of the daughter cell being anucleate and the other one containing a diploid nucleus [10]. Typically, such events are lethal for at least one of the daughter cells.…”

Section: Introductionmentioning

confidence: 99%

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

Zemlianski,

Marešová,

Princová

et al. 2023

Preprint

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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 yeastSchizosaccharomyces pombemay 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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Section: Introductionmentioning

confidence: 99%

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

Zemlianski,

Marešová,

Princová

et al. 2023

Preprint

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show abstract

Section: Discussionmentioning

confidence: 99%

“…Other dense material in the vicinity of the division plane may prevent the nucleus from reaching the contractile ring. The actin network of the contractile ring is a possible candidate that can exert forces against the nucleus and influence its position (Yukawa et al ., 2021). Alternatively, connections between the nuclear envelope and the plasma membrane, such as the cortical endoplasmic reticulum, may slow down the displacement of the nucleus (Zhang et al ., 2010).…”

Section: Discussionmentioning

confidence: 99%

Microtubule competition and cell growth recenter the nucleus after anaphase in fission yeast

Bellingham-Johnstun¹,

Thorn²,

Belmonte³

et al. 2023

Preprint

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Cells actively position their nucleus based on their activity. In fission yeast, microtubule-dependent nuclear centering is critical for symmetrical cell division. After spindle disassembly at the end of anaphase, the nucleus recenters over a ~90 min period, approximately half of the duration of the cell cycle. Live cell and simulation experiments support the cooperation of two distinct mechanisms in the slow recentering of the nucleus. First, a push-push mechanism acts from spindle disassembly to septation and involves the opposing actions of the mitotic Spindle Pole Body microtubules that push the nucleus away from the ends of the cell while post-anaphase array of microtubules basket the nucleus and limit its migration toward the division plane. Second, a slow-and-grow mechanism finalizes nuclear centering in the newborn cell. In this mechanism, microtubule competition stalls the nucleus while asymmetric cell growth slowly centers it. Our work underlines how intrinsic properties of microtubules differently impact nuclear positioning according to microtubule network organization and cell size.

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“…Instead, the nucleus seems to be pushed to one side of the cell, giving rise to an anucleated compartment and a compartment retaining the undivided nucleus. Recently, work from the Toda laboratory has uncovered a mechanism that facilitates the drifting of the nucleus in order to prevent “cutting” of the DNA and mitotic catastrophe ( Yukawa et al, 2021 ). This process, that is highly dependent on the actin cytoskeleton, reinforces the idea that evolution has developed alternative mechanisms to give cells a last chance of survival when the final step in the cell cycle, mitosis, cannot be completed.…”

Section: Discussionmentioning

confidence: 99%

Uncoupling of Mitosis and Cytokinesis Upon a Prolonged Arrest in Metaphase Is Influenced by Protein Phosphatases and Mitotic Transcription in Fission Yeast

Chica

Portantier

Nyquist-Andersen

et al. 2022

Front. Cell Dev. Biol.

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Depletion of the Anaphase-Promoting Complex/Cyclosome (APC/C) activator Cdc20 arrests cells in metaphase with high levels of the mitotic cyclin (Cyclin B) and the Separase inhibitor Securin. In mammalian cells this arrest has been exploited for the treatment of cancer with drugs that engage the spindle assembly checkpoint and, recently, with chemical inhibitors of the APC/C. While most cells arrested in mitosis for prolonged periods undergo apoptosis, others skip cytokinesis and enter G1 with unsegregated chromosomes. This process, known as mitotic slippage, generates aneuploidy and increases genomic instability in the cancer cell. Here, we analyze the behavior of fission yeast cells arrested in mitosis through the transcriptional silencing of the Cdc20 homolog slp1. While depletion of slp1 readily halts cells in metaphase, this arrest is only transient and a majority of cells eventually undergo cytokinesis and show steady mitotic dephosphorylation. Notably, this occurs in the absence of Cyclin B (Cdc13) degradation. We investigate the involvement of phosphatase activity in these events and demonstrate that PP2A-B55Pab1 is required to prevent septation and, during the arrest, its CDK-mediated inhibition facilitates the induction of cytokinesis. In contrast, deletion of PP2A-B56Par1 completely abrogates septation. We show that this effect is partly due to this mutant entering mitosis with reduced CDK activity. Interestingly, both PP2A-B55Pab1 and PP2A-B56Par1, as well as Clp1 (the homolog of the budding yeast mitotic phosphatase Cdc14) are required for the dephosphorylation of mitotic substrates during the escape. Finally, we show that the mitotic transcriptional wave controlled by the RFX transcription factor Sak1 facilitates the induction of cytokinesis and also requires the activity of PP2A-B56Par1 in a mechanism independent of CDK.

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Escape from mitotic catastrophe by actin-dependent nuclear displacement in fission yeast

Cited by 8 publications

References 60 publications

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

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

Microtubule competition and cell growth recenter the nucleus after anaphase in fission yeast

Uncoupling of Mitosis and Cytokinesis Upon a Prolonged Arrest in Metaphase Is Influenced by Protein Phosphatases and Mitotic Transcription in Fission Yeast

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