Fission yeast Wee1 is required for stable kinetochore-microtubule attachment
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2024 Jan;14(1):230379.
doi: 10.1098/rsob.230379.
Epub 2024 Jan 3.
Masahiro Takado  1 ,
Takaharu G Yamamoto  2 ,
Yuji Chikashige  2 ,
Tomohiro Matsumoto  1
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Affiliations
1 Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.
2 Kobe Frontier Research Center, Advanced ICT Research Institute, National Institute of Information and Communications Technology, Kobe 651-2492, Japan.
PMID: 38166399
PMCID: PMC10762435
DOI: 10.1098/rsob.230379
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Masahiro Takado  et al.
Open Biol .
2024 Jan .
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2024 Jan;14(1):230379.
doi: 10.1098/rsob.230379.
Epub 2024 Jan 3.
Authors
Masahiro Takado  1 ,
Takaharu G Yamamoto  2 ,
Yuji Chikashige  2 ,
Tomohiro Matsumoto  1
Affiliations
1 Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.
2 Kobe Frontier Research Center, Advanced ICT Research Institute, National Institute of Information and Communications Technology, Kobe 651-2492, Japan.
PMID: 38166399
PMCID: PMC10762435
DOI: 10.1098/rsob.230379
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Abstract
Wee1 is a cell cycle regulator that phosphorylates Cdk1/Cdc2 and inhibits G2/M transition. Loss of Wee1 in fission yeast results in an early onset of mitosis. Interestingly, we found that cells lacking Wee1 require the functional spindle checkpoint for their viability. Genetic analysis indicated that the requirement is not attributable to the early onset of mitosis. Live-cell imaging revealed that some kinetochores are not attached or bioriented in the wee1 mutant. Furthermore, Mad2, a component of the spindle checkpoint known to recognize unattached kinetochores, accumulates in the vicinity of the spindle, representing activation of the spindle checkpoint in the mutant. It appears that the wee1 mutant cannot maintain stable kinetochore-microtubule attachment, and relies on the delay imposed by the spindle checkpoint for establishing biorientation of kinetochores. This study revealed a role of Wee1 in ensuring accurate segregation of chromosomes during mitosis, and thus provided a basis for a new principle of cancer treatment with Wee1 inhibitors.
Keywords: Wee1; fission yeast; kinetochore; mitosis; spindle checkpoint.
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Conflict of interest statement
We declare we have no competing interests.
Figures
Figure 1.
Kinetochore-microtubule attachment is not stable…
Figure 1.
Kinetochore-microtubule attachment is not stable in the wee1 mutants. Time-lapse images were taken…
Figure 2.
The onset of anaphase is…
Figure 2.
The onset of anaphase is delayed in the wee1 mutants. The time-lapse images…
Figure 3.
The spindle checkpoint is activated…
Figure 3.
The spindle checkpoint is activated in the wee1 mutants. Time-lapse images were taken…
Figure 4.
The activation of spindle checkpoint…
Figure 4.
The activation of spindle checkpoint delays anaphase onset in the wee1 mutants. (…
Figure 5.
Unequal chromosome segregation in the…
Figure 5.
Unequal chromosome segregation in the wee1-50 mutant lacking Mad2. ( a ) The…
See this image and copyright information in PMC
References
Kellogg DR. 2003. Wee1-dependent mechanisms required for coordination of cell growth and cell division. J. Cell Sci. 116, 4883-4890. (10.1242/jcs.00908) - DOI - PubMed
Wood E, Nurse P. 2015. Sizing up to divide: mitotic cell-size control in fission yeast. Annu. Rev. Cell Dev. Biol. 31, 11-29. (10.1146/annurev-cellbio-100814-125601) - DOI - PubMed
Nurse P. 1975. Genetic control of cell size at cell division in yeast. Nature 256, 547-551. (10.1038/256547a0) - DOI - PubMed
Thuriaux P, Nurse P, Carter B. 1978. Mutants altered in the control co-ordinating cell division with cell growth in the fission yeast Schizosaccharomyces pombe. Mol. Gen. Genet. 161, 215-220. (10.1007/BF00274190) - DOI - PubMed
Fantes PA. 1981. Isolation of cell size mutants of a fission yeast by a new selective method: characterization of mutants and implications for division control mechanisms. J. Bacteriol. 146, 746-754. (10.1128/jb.146.2.746-754.1981) - DOI - PMC - PubMed
MeSH terms
Cell Cycle Proteins / genetics Actions Search in PubMed Search in MeSH Add to Search
Cell Cycle Proteins / metabolism Actions Search in PubMed Search in MeSH Add to Search
Kinetochores / metabolism Actions Search in PubMed Search in MeSH Add to Search
Microtubules / metabolism Actions Search in PubMed Search in MeSH Add to Search
Mitosis Actions Search in PubMed Search in MeSH Add to Search
Nuclear Proteins / genetics Actions Search in PubMed Search in MeSH Add to Search
Nuclear Proteins / metabolism Actions Search in PubMed Search in MeSH Add to Search
Protein-Tyrosine Kinases / genetics Actions Search in PubMed Search in MeSH Add to Search
Protein-Tyrosine Kinases / metabolism Actions Search in PubMed Search in MeSH Add to Search
Schizosaccharomyces pombe Proteins* / genetics Actions Search in PubMed Search in MeSH Add to Search
Schizosaccharomyces pombe Proteins* / metabolism Actions Search in PubMed Search in MeSH Add to Search
Schizosaccharomyces* / genetics Actions Search in PubMed Search in MeSH Add to Search
Schizosaccharomyces* / metabolism Actions Search in PubMed Search in MeSH Add to Search
Spindle Apparatus / metabolism Actions Search in PubMed Search in MeSH Add to Search
Substances
Cell Cycle Proteins Actions Search in PubMed Search in MeSH Add to Search
Nuclear Proteins Actions Search in PubMed Search in MeSH Add to Search
wee1 protein, S pombe Actions Search in PubMed Search in MeSH Add to Search
Protein-Tyrosine Kinases Actions Search in PubMed Search in MeSH Add to Search
Schizosaccharomyces pombe Proteins Actions Search in PubMed Search in MeSH Add to Search
Related information
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Search in PubMed. Search in NLM Catalog. Add to Search. . 2024 Jan;14(1):230379. doi: 10.1098/rsob.230379. Epub 2024 Jan 3. Masahiro Takado  1 , Takaharu G Yamamoto  2 , Yuji Chikashige  2 , Tomohiro Matsumoto  1. Expand. Affiliations. 1 Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan. 2 Kobe Frontier Research Center, Advanced ICT Research Institute, National Institute of Information and Communications Technology, Kobe 651-2492, Japan. PMID: 38166399. PMCID: PMC10762435. DOI: 10.1098/rsob.230379. Free PMC article. Masahiro Takado  et al. Open Biol . 2024 Jan . Free PMC article. Show details. Display options. Format. Search in PubMed. Search in NLM Catalog. Add to Search. . 2024 Jan;14(1):230379. doi: 10.1098/rsob.230379. Epub 2024 Jan 3. Authors. Masahiro Takado  1 , Takaharu G Yamamoto  2 , Yuji Chikashige  2 , Tomohiro Matsumoto  1. Affiliations. 1 Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan. 2 Kobe Frontier Research Center, Advanced ICT Research Institute, National Institute of Information and Communications Technology, Kobe 651-2492, Japan. PMID: 38166399. PMCID: PMC10762435. DOI: 10.1098/rsob.230379. Cite. Display options. Format. Abstract. Wee1 is a cell cycle regulator that phosphorylates Cdk1/Cdc2 and inhibits G2/M transition. Loss of Wee1 in fission yeast results in an early onset of mitosis. Interestingly, we found that cells lacking Wee1 require the functional spindle checkpoint for their viability. Genetic analysis indicated that the requirement is not attributable to the early onset of mitosis. Live-cell imaging revealed that some kinetochores are not attached or bioriented in the wee1 mutant. Furthermore, Mad2, a component of the spindle checkpoint known to recognize unattached kinetochores, accumulates in the vicinity of the spindle, representing activation of the spindle checkpoint in the mutant. It appears that the wee1 mutant cannot maintain stable kinetochore-microtubule attachment, and relies on the delay imposed by the spindle checkpoint for establishing biorientation of kinetochores. This study revealed a role of Wee1 in ensuring accurate segregation of chromosomes during mitosis, and thus provided a basis for a new principle of cancer treatment with Wee1 inhibitors. Keywords: Wee1; fission yeast; kinetochore; mitosis; spindle checkpoint. PubMed Disclaimer. Conflict of interest statement. We declare we have no competing interests. Figures. Figure 1. Kinetochore-microtubule attachment is not stable… Figure 1. Kinetochore-microtubule attachment is not stable in the wee1 mutants. Time-lapse images were taken… Figure 2. The onset of anaphase is… Figure 2. The onset of anaphase is delayed in the wee1 mutants. The time-lapse images… Figure 3. The spindle checkpoint is activated… Figure 3. The spindle checkpoint is activated in the wee1 mutants. Time-lapse images were taken… Figure 4. The activation of spindle checkpoint… Figure 4. The activation of spindle checkpoint delays anaphase onset in the wee1 mutants. (… Figure 5. Unequal chromosome segregation in the… Figure 5. Unequal chromosome segregation in the wee1-50 mutant lacking Mad2. ( a ) The… See this image and copyright information in PMC. References. Kellogg DR. 2003. Wee1-dependent mechanisms required for coordination of cell growth and cell division. J. Cell Sci. 116, 4883-4890. (10.1242/jcs.00908) - DOI - PubMed. Wood E, Nurse P. 2015. Sizing up to divide: mitotic cell-size control in fission yeast. Annu. Rev. Cell Dev. Biol. 31, 11-29. (10.1146/annurev-cellbio-100814-125601) - DOI - PubMed. Nurse P. 1975. Genetic control of cell size at cell division in yeast. Nature 256, 547-551. (10.1038/256547a0) - DOI - PubMed. Thuriaux P, Nurse P, Carter B. 1978. Mutants altered in the control co-ordinating cell division with cell growth in the fission yeast Schizosaccharomyces pombe. Mol. Gen. Genet. 161, 215-220. (10.1007/BF00274190) - DOI - PubMed. Fantes PA. 1981. Isolation of cell size mutants of a fission yeast by a new selective method: characterization of mutants and implications for division control mechanisms. J. Bacteriol. 146, 746-754. (10.1128/jb.146.2.746-754.1981) - DOI - PMC - PubMed. MeSH terms. Cell Cycle Proteins / genetics Actions Search in PubMed Search in MeSH Add to Search. Cell Cycle Proteins / metabolism Actions Search in PubMed Search in MeSH Add to Search. Kinetochores / metabolism Actions Search in PubMed Search in MeSH Add to Search. Microtubules / metabolism Actions Search in PubMed Search in MeSH Add to Search. Mitosis Actions Search in PubMed Search in MeSH Add to Search. Nuclear Proteins / genetics Actions Search in PubMed Search in MeSH Add to Search. Nuclear Proteins / metabolism Actions Search in PubMed Search in MeSH Add to Search. Protein-Tyrosine Kinases / genetics Actions Search in PubMed Search in MeSH Add to Search. Protein-Tyrosine Kinases / metabolism Actions Search in PubMed Search in MeSH Add to Search. Schizosaccharomyces pombe Proteins* / genetics Actions Search in PubMed Search in MeSH Add to Search. Schizosaccharomyces pombe Proteins* / metabolism Actions Search in PubMed Search in MeSH Add to Search. Schizosaccharomyces* / genetics Actions Search in PubMed Search in MeSH Add to Search. Schizosaccharomyces* / metabolism Actions Search in PubMed Search in MeSH Add to Search. Spindle Apparatus / metabolism Actions Search in PubMed Search in MeSH Add to Search. Substances. Cell Cycle Proteins Actions Search in PubMed Search in MeSH Add to Search. Nuclear Proteins Actions Search in PubMed Search in MeSH Add to Search. wee1 protein, S pombe Actions Search in PubMed Search in MeSH Add to Search. Protein-Tyrosine Kinases Actions Search in PubMed Search in MeSH Add to Search. Schizosaccharomyces pombe Proteins Actions Search in PubMed Search in MeSH Add to Search. Related information. MedGen. LinkOut - more resources. Full Text Sources Atypon. Miscellaneous NCI CPTAC Assay Portal.