Fission yeast Wee1 is required for stable kinetochore-microtubule attachment

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 tha...

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Bibliographic Details
Published in:Open biology 2024-01, Vol.14 (1), p.230379-7
Main Authors: Takado, Masahiro, Yamamoto, Takaharu G, Chikashige, Yuji, Matsumoto, Tomohiro
Format: Article
Language:English
Subjects:
Cancer therapies
Cdc2 protein
Cell cycle
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Cell division
Chromosomes
Cyclin-dependent kinases
fission yeast
Genetic analysis
Kinases
kinetochore
Kinetochores
Kinetochores - metabolism
Microtubules - metabolism
Mitosis
Mutants
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Protein-Tyrosine Kinases - genetics
Protein-Tyrosine Kinases - metabolism
Schizosaccharomyces - genetics
Schizosaccharomyces - metabolism
Schizosaccharomyces pombe Proteins - genetics
Schizosaccharomyces pombe Proteins - metabolism
Spindle Apparatus - metabolism
spindle checkpoint
Surveillance
Wee1
Yeast
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Summary: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 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 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.
ISSN:2046-2441
2046-2441
DOI:10.1098/rsob.230379