RRC ID 78051
Author Takado M, Yamamoto TG, Chikashige Y, Matsumoto T.
Title Fission yeast Wee1 is required for stable kinetochore-microtubule attachment.
Journal Open Biol
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.
Volume 14(1)
Pages 230379
Published 2024-1-1
DOI 10.1098/rsob.230379
PMID 38166399
PMC PMC10762435
MeSH Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Kinetochores / metabolism Microtubules / metabolism Mitosis 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