The content discusses the bistable nature of the mitotic control system in fission yeast cells. Key highlights:
Eukaryotic cell division cycle (G1-S-G2-M) is maintained by irreversible transitions governed by bistable switching mechanisms at key checkpoints.
The authors developed a computational model of the mitotic control system in fission yeast, which includes the regulation of cyclin-dependent kinase (CDK) by inhibitory kinases (Wee1/Mik1) and activating phosphatase (Cdc25).
Stochastic simulations of the model show that the dose-response curves of CDK activity versus fusion protein (non-degradable cyclin) level exhibit bistability, with cells existing in either a low (interphase) or high (mitotic) CDK activity state.
The bistable behavior is dependent on cell size, with larger cells activating CDK at lower fusion protein levels compared to smaller cells.
The authors argue that the experimental data of Patterson et al. (2021) only probed the activation side of the bistable switch and did not provide unequivocal evidence for bistability, as the observations could also be explained by a reversible, size-dependent sigmoidal switch.
To conclusively demonstrate bistability, the authors propose a modified experimental protocol using degradable fusion protein, which would allow observing both the activation and inactivation thresholds of the mitotic switch.
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by Novak,B., Ty... at www.biorxiv.org 01-24-2024
https://www.biorxiv.org/content/10.1101/2024.01.23.576917v1Deeper Inquiries