The internal loop of fission yeast Ndc80 binds Alp7/TACC-Alp14/TOG and ensures proper chromosome attachment

Tang, Ningning; Takada, Hirofumi; Hsu, Kuo-Shun; Toda, Takashi

doi:10.1091/mbc.e12-11-0817

Cited by 50 publications

(80 citation statements)

References 97 publications

(160 reference statements)

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“…Because spindle assembly can occur in the absence of chromosomes ( 101 ) and fission-yeast mutants defective in kinetochore-MT attachments can still assemble bipolar spindles ( 89 , 92 , 98 ), we have neglected any mechanical contributions of chromosomes. The effects of kinetochore-MT attachments on MT dynamics ( 23 , 25 , 114 ) are implicitly modeled through our optimization of MT dynamics for spindle stability.…”

Section: Resultsmentioning

confidence: 99%

Physical determinants of bipolar mitotic spindle assembly and stability in fission yeast

et al. 2017

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Section: Resultsmentioning

confidence: 99%

Physical determinants of bipolar mitotic spindle assembly and stability in fission yeast

et al. 2017

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“…Because spindle assembly can occur in the absence of chromosomes (101) and fission-yeast mutants defective in kinetochore-MT attachments can still assemble bipolar spindles (89,92,98), we have neglected any mechanical contributions of chromosomes. The effects of kinetochore-MT attachments on MT dynamics (23,25,114) are implicitly modeled through our optimization of MT dynamics for spindle stability.…”

Section: Modelmentioning

confidence: 99%

“…We have used biophysical modeling and quantification of spindle assembly in a cell type that is both relatively simple and amenable to experimental modification, the fission yeast Schizosaccharomyces pombe. This organism has previously been studied in enough detail to allow formulation of a realistic model (78,79); it is small enough that detailed three-dimensional simulations are computationally tractable (80); it is amenable to the genetic manipulation and quantitative experiments needed to parameterize the model (5,6,11,19,20,22,(81)(82)(83)(84)(85)(86)(87)(88)(89)(90)(91)(92)(93)(94)(95)(96)(97)(98); and the cell contains only three chromosomes whose separate motions can be imaged. Unlike the situation in budding yeast, the mitotic spindle of S. pombe shows important similarities to that of metazoans: Spindle assembly begins in mitotic prophase, and kinetochores attach multiple MTs.…”

Section: Introductionmentioning

confidence: 99%

Physical Determinants of Bipolar Mitotic Spindle Assembly and Stability in Fission Yeast

Betterton

Blackwell

Edelmaier

et al. 2017

Biophysical Journal

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Mitotic spindles use an elegant bipolar architecture to segregate duplicated chromosomes with high fidelity. Bipolar spindles form from a monopolar initial condition; this is the most fundamental construction problem that the spindle must solve. Microtubules, motors, and cross-linkers are important for bipolarity, but the mechanisms necessary and sufficient for spindle assembly remain unknown. We describe a physical model that exhibits de novo bipolar spindle formation. We began with physical properties of fission-yeast spindle pole body size and microtubule number, kinesin-5 motors, kinesin-14 motors, and passive cross-linkers. Our model results agree quantitatively with our experiments in fission yeast, thereby establishing a minimal system with which to interrogate collective selfassembly. By varying the features of our model, we identify a set of functions essential for the generation and stability of spindle bipolarity. When kinesin-5 motors are present, their bidirectionality is essential, but spindles can form in the presence of passive cross-linkers alone. We also identify characteristic failed states of spindle assemblythe persistent monopole, X spindle, separated asters, and short spindle, which are avoided by the creation and maintenance of antiparallel microtubule overlaps. Our model can guide the identification of new, multifaceted strategies to induce mitotic catastrophes; these would constitute novel strategies for cancer chemotherapy.

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“…Our results suggest there is a defect in kinetochore-microtubule attachment in the prometaphase-arrested pot1⌬ rqh1-hd double mutant. If this is true, kinetochores should continue to move between the two SPBs (39). To test this, we examined the localization of the kinetochore in pot1⌬ rqh1-hd double mutants expressing Mis12-GFP (a kinetochore marker [40]) and mCherry-Atb2.…”

Section: Resultsmentioning

confidence: 99%

Rad51-Dependent Aberrant Chromosome Structures at Telomeres and Ribosomal DNA Activate the Spindle Assembly Checkpoint

Nakano

Masuda

Hiromoto

et al. 2014

Molecular and Cellular Biology

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bThe spindle assembly checkpoint (SAC) monitors defects in kinetochore-microtubule attachment or lack of tension at kinetochores and arrests cells at prometaphase. In fission yeast, the double mutant between pot1⌬ and the helicase-dead point mutant of the RecQ helicase Rqh1 gene (rqh1-hd) accumulates Rad51-dependent recombination intermediates at telomeres and enters mitosis with those intermediates. Here, we found that SAC-dependent prometaphase arrest occurred more frequently in pot1⌬ rqh1-hd double mutants than in rqh1-hd single mutants. SAC-dependent prometaphase arrest also occurred more frequently in rqh1-hd single mutants after cells were released from DNA replication block compared to the rqh1-hd single mutant in the absence of exogenous insult to the DNA. In both cases, Mad2 foci persisted longer than usual at kinetochores, suggesting a defect in kinetochore-microtubule attachment. In pot1⌬ rqh1-hd double mutants and rqh1-hd single mutants released from DNA replication block, SAC-dependent prometaphase arrest was suppressed by the removal of the recombination or replication intermediates. Our results indicate that the accumulation of recombination or replication intermediates induces SAC-dependent prometaphase arrest, possibly by affecting kinetochore-microtubule attachment.

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The internal loop of fission yeast Ndc80 binds Alp7/TACC-Alp14/TOG and ensures proper chromosome attachment

Cited by 50 publications

References 97 publications

Physical determinants of bipolar mitotic spindle assembly and stability in fission yeast

Physical determinants of bipolar mitotic spindle assembly and stability in fission yeast

Physical Determinants of Bipolar Mitotic Spindle Assembly and Stability in Fission Yeast

Rad51-Dependent Aberrant Chromosome Structures at Telomeres and Ribosomal DNA Activate the Spindle Assembly Checkpoint

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