ArticleProceedings of the National Academy of Sciences of the United States of America2005
Evaluating putative mechanisms of the mitotic spindle checkpoint.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Network architecture determines delay robustness in the spindle assembly checkpoint.Scientific reports · 2026Article
- Delayed Signaling in Mitotic Checkpoints: Biological Mechanisms and Modeling Perspectives.Biology · 2026Review
- Artificial intelligence in mitotic checkpoint modeling: transforming our understanding of cellular division through machine learning and predictive biology.Briefings in bioinformatics · 2026Review
- A minimal deterministic model reveals integration of spindle assembly and position checkpoints in mitosis.Scientific reports · 2025Article
- Dynamics of spindle assembly and position checkpoints: Integrating molecular mechanisms with computational models.Computational and structural biotechnology journal · 2025Review
- Cell Cycle Complexity: Exploring the Structure of Persistent Subsystems in 414 Models.Biomedicines · 2024Article
- Multi-scale stochastic organization-oriented coarse-graining exemplified on the human mitotic checkpoint.Scientific reports · 2019Article
- Implications of alternative routes to APC/C inhibition by the mitotic checkpoint complex.PLoS computational biology · 2018Article
- A Dynamical Model for Activating and Silencing the Mitotic Checkpoint.Scientific reports · 2017Article
- A Cell Biological Perspective on Past, Present and Future Investigations of the Spindle Assembly Checkpoint.Biology · 2016Review
- Dual mechanisms regulate the recruitment of spindle assembly checkpoint proteins to the budding yeast kinetochore.Molecular biology of the cell · 2016Article
- Coupling changes in cell shape to chromosome segregation.Nature reviews. Molecular cell biology · 2016Review
- The mitotic checkpoint complex (MCC): looking back and forth after 15 years.AIMS molecular science · 2016Article
- Erroneous Silencing of the Mitotic Checkpoint by Aberrant Spindle Pole-Kinetochore Coordination.Biophysical journal · 2015Article
- Systems Biology Modeling of Five Pathways for Regulation and Potent Inhibition of the Anaphase-Promoting Complex (APC/C): Pivotal Roles for MCC and BubR1.Omics : a journal of integrative biology · 2015Article
- Spindle assembly checkpoint is sufficient for complete Cdc20 sequestering in mitotic control.Computational and structural biotechnology journal · 2015Article
- Active transport can greatly enhance Cdc20:Mad2 formation.International journal of molecular sciences · 2014Article
- Spatial-temporal model for silencing of the mitotic spindle assembly checkpoint.Nature communications · 2014Article
- Catalytic assembly of the mitotic checkpoint inhibitor BubR1-Cdc20 by a Mad2-induced functional switch in Cdc20.Molecular cell · 2013Article
- Spatial rule-based modeling: a method and its application to the human mitotic kinetochore.Cells · 2013Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mitotic spindle checkpoint halts the cell cycle until all chromosomes are attached to the mitotic spindles. Evidence suggests that the checkpoint prevents cell-cycle progression by inhibiting the activity of the APC-Cdc20 complex, but the precise mechanism underlying this inhibition is not yet known. Here, we use mathematical modeling to compare several mechanisms that could account for this inhibition. We describe the interplay between the capacities to strongly inhibit cell-cycle progression before spindle attachment on one hand and to rapidly resume cell-cycle progression once the last kinetochore is attached on the other hand. We find that inhibition that is restricted to the kinetochore region is not sufficient for supporting both requirements when realistic diffusion constants are considered. A mechanism that amplifies the checkpoint signal through autocatalyzed inhibition is also insufficient. In contrast, amplifying the signal through the release of a diffusible inhibitory complex can support reliable checkpoint function. Our results suggest that the design of the spindle checkpoint network is limited by physical constraints imposed by realistic diffusion constants and the relevant spatial and temporal dimensions where computation is performed.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.