ArticleProceedings of the National Academy of Sciences of the United States of America2000
Modeling the fission yeast cell cycle: quantized cycle times in wee1- cdc25Delta mutant cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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36 citing papers in PubMed, 122 citations in OpenAlex.
- Capturing CDKs in action: Live-cell biosensors pioneer the new frontiers in cell cycle research.Cell structure and function · 2025Review
- A Tetracycline-Inducible Promoter Replacement System formicroPublication biology · 2025Article
- Implications of differential size-scaling of cell-cycle regulators on cell size homeostasis.PLoS computational biology · 2023Article
- Uncoupling of Mitosis and Cytokinesis Upon a Prolonged Arrest in Metaphase Is Influenced by Protein Phosphatases and Mitotic Transcription in Fission Yeast.Frontiers in cell and developmental biology · 2022Article
- Modeling the Control of Meiotic Cell Divisions: Entry, Progression, and Exit.Biophysical journal · 2020Article
- Article
- An agent-based model of the fission yeast cell cycle.Current genetics · 2019Article
- Quantitative Studies for Cell-Division Cycle Control.Frontiers in physiology · 2019Review
- Adding phosphorylation events to the core oscillator driving the cell cycle of fission yeast.PloS one · 2018Article
- Time-lapse electrical impedance spectroscopy for monitoring the cell cycle of single immobilized S. pombe cells.Scientific reports · 2015Article
- From START to FINISH: computational analysis of cell cycle control in budding yeast.NPJ systems biology and applications · 2015Article
- Neutral space analysis for a Boolean network model of the fission yeast cell cycle network.Biological research · 2014Article
- Article
- Model discrimination in dynamic molecular systems: application to parotid de-differentiation network.Journal of computational biology : a journal of computational molecular cell biology · 2013Article
- Article
- Robust cell size checkpoint from spatiotemporal positive feedback loop in fission yeast.BioMed research international · 2013Article
- Article
- Overexpression limits of fission yeast cell-cycle regulators in vivo and in silico.Molecular systems biology · 2011Article
- Mathematical modeling of fission yeast Schizosaccharomyces pombe cell cycle: exploring the role of multiple phosphatases.Systems and synthetic biology · 2011Article
- Process-based network decomposition reveals backbone motif structure.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
A detailed mathematical model for the fission yeast mitotic cycle is developed based on positive and negative feedback loops by which Cdc13/Cdc2 kinase activates and inactivates itself. Positive feedbacks are created by Cdc13/Cdc2-dependent phosphorylation of specific substrates: inactivating its negative regulators (Rum1, Ste9 and Wee1/Mik1) and activating its positive regulator (Cdc25). A slow negative feedback loop is turned on during mitosis by activation of Slp1/anaphase-promoting complex (APC), which indirectly re-activates the negative regulators, leading to a drop in Cdc13/Cdc2 activity and exit from mitosis. The model explains how fission yeast cells can exit mitosis in the absence of Ste9 (Cdc13 degradation) and Rum1 (an inhibitor of Cdc13/Cdc2). We also show that, if the positive feedback loops accelerating the G(2)/M transition (through Wee1 and Cdc25) are weak, then cells can reset back to G(2) from early stages of mitosis by premature activation of the negative feedback loop. This resetting can happen more than once, resulting in a quantized distribution of cycle times, as observed experimentally in wee1(-) cdc25Delta mutant cells. Our quantitative description of these quantized cycles demonstrates the utility of mathematical modeling, because these cycles cannot be understood by intuitive arguments alone.
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