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Updated: May 29, 2025
Examination of Mitotic and Meiotic Fission Yeast Nuclear Dynamics by Fluorescence Live-cell Microscopy
Published on: June 24, 2019
S. pombe Mis4 is required for exit from G0 as it is necessary for full nuclear separation during the subsequent M
Michiko Suma1, Orie Arakawa2, Yuria Tahara2
1Institute of Life Science, Kurume University, Asahi-machi 67, Kurume, Fukuoka 830-0011, Japan.
Abstract:
The evolutionarily conserved Mis4 protein establishes cohesion between replicated sister chromatids in vegetatively proliferating cells. In the fission yeast, Schizosaccharomyces pombe, defects in Mis4 lead to premature separation of sister chromatids, resulting in fatal chromosome mis-segregation during mitosis. In humans, NIPBL, an ortholog of Mis4, is responsible for a multisystem disorder called Cornelia de Lange syndrome. We have previously reported that Mis4 is also essential in non-proliferating quiescent cells. Whereas wild-type fission yeast cells can maintain high viability for long periods without cell division in the quiescent G0 phase, mis4-450 mutant cells cannot. Here, we show that Mis4 is not required for cells to enter G0 phase, but is essential for them to exit from it. When resuming mitosis after a passage of G0, mis4 mutant cells segregated sister chromatids successfully, but failed to separate daughter nuclei completely and consequently formed dikaryon-like cells. These findings suggest a novel role for Mis4/NIPBL in quiescent cells, which is a prerequisite for full nuclear separation upon resumed mitosis. As most human cells are in a quiescent state, this study might facilitate development of novel therapies for human diseases caused by Mis4/NIPBL deficiency.
Insights
The Mis4 protein is crucial for cell division exit from quiescence. Mutations impair nuclear separation in fission yeast, offering insights into Cornelia de Lange syndrome therapies.
Area of Science:
- Cell Biology
- Genetics
- Molecular Biology
Background:
- Mis4 protein ensures sister chromatid cohesion in dividing cells.
- Defects in Mis4 cause chromosome mis-segregation and are linked to Cornelia de Lange syndrome.
- Mis4 is also vital for non-proliferating quiescent cells.
Purpose of the Study:
- To investigate the role of Mis4 in quiescent fission yeast cells.
- To determine Mis4's function during the exit from G0 phase.
- To understand the consequences of Mis4 deficiency in nuclear division after quiescence.
Main Methods:
- Utilizing the fission yeast Schizosaccharomyces pombe model system.
- Analyzing mis4-450 mutant cells during entry and exit from G0 phase.
- Observing nuclear morphology and cell division post-quiescence.
Main Results:
- Mis4 is not required for entering G0 phase but is essential for exiting it.
- Mis4-deficient cells successfully segregate sister chromatids but fail in complete daughter nucleus separation.
- Dikaryon-like cell formation observed in mis4 mutant cells after G0 exit.
Conclusions:
- Mis4/NIPBL has a novel role in facilitating nuclear separation upon resuming mitosis from quiescence.
- This function is critical for cell viability and proper division after a period of non-proliferation.
- Findings may inform therapeutic strategies for Mis4/NIPBL-related human disorders, given that most human cells are quiescent.
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