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Reconstitution of Cell-cycle Oscillations in Microemulsions of Cell-free Xenopus Egg Extracts
Published on: September 27, 2018
The Cdk1-APC/C cell cycle oscillator circuit functions as a time-delayed, ultrasensitive switch
1Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305-5174, USA.
Nature Cell Biology
|April 30, 2013
Summary
Biological oscillators use negative feedback loops. This study reveals the Xenopus laevis cell cycle oscillator functions as a time-delayed, ultrasensitive switch, generating robust cell cycle oscillations.
Area of Science:
- Cellular biology
- Systems biology
- Biophysics
Background:
- Biological oscillators are fundamental to life, relying on negative feedback loops.
- The Xenopus laevis embryonic cell cycle features a core negative feedback loop involving cyclin B-Cdk1 kinase and APC/C(Cdc20) ubiquitin ligase.
Purpose of the Study:
- To quantitatively analyze the negative feedback loop in the Xenopus laevis cell cycle oscillator.
- To understand the mechanisms preventing a stable steady state in the Cdk1-APC/C(Cdc20) system.
Main Methods:
- Quantitative analysis of the Cdk1-APC/C(Cdc20) feedback loop.
- Computational modeling of the oscillator system.
Main Results:
- The system operates as a time-delayed, digital switch with a significant lag (∼15 min) between Cdk1 and APC/C(Cdc20) activation.
- The oscillator exhibits a high degree of ultrasensitivity (Hill coefficient n(H)≈17).
- These attributes are crucial for generating robust, clock-like oscillations.
Conclusions:
- The quantitative properties of the negative feedback loop, specifically time delay and ultrasensitivity, are key to robust biological oscillations.
- These principles may inform the design of synthetic biological clocks and apply to other activator-repressor oscillator systems.
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