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Barberis M  (2012) Sic1 as a timer of Clb cyclin waves in the yeast cell cycle--design principle of not just an inhibitor. FEBS J 279(18):3386-410

Abstract: Cellular systems biology aims to uncover design principles that describe the properties of biological networks through interaction of their components in space and time. The cell cycle is a complex system regulated by molecules that are integrated into functional modules to ensure genome integrity and faithful cell division. In budding yeast, cyclin-dependent kinases (Cdk1/Clb) drive cell cycle progression, being activated and inactivated in a precise temporal sequence. In this module, which we refer to as the 'Clb module', different Cdk1/Clb complexes are regulated to generate waves of Clb activity, a functional property of cell cycle control. The inhibitor Sic1 plays a critical role in the Clb module by binding to and blocking Cdk1/Clb activity, ultimately setting the timing of DNA replication and mitosis. Fifteen years of research subsequent to the identification of Sic1 have lead to the development of an integrative approach that addresses its role in regulating the Clb module. Sic1 is an intrinsically disordered protein and achieves its inhibitory function by cooperative binding, where different structural regions stretch on the Cdk1/Clb surface. Moreover, Sic1 promotes S phase entry, facilitating Cdk1/Clb5 nuclear transport, and therefore revealing a double function of inhibitor/activator that rationalizes a mechanism to prevent precocious DNA replication. Interestingly, the investigation of Clb temporal dynamics by mathematical modelling and experimental validation provides evidence that Sic1 acts as a timer to coordinate oscillations of Clb cyclin waves. Here we review these findings, focusing on the design principle underlying the Clb module, which highlights the role of Sic1 in regulating phase-specific Cdk1/Clb activities.

Status: Published Type: Journal Article PubMed ID: 22356687

Topics addressed in this paper

Number of different genes curated to this paper: 29

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Topics Genes linked to topics (#1 - 10 )
ACE2 CDC14 CDC28 CDC34 CDC4 CDC53 CDH1 CLB1 CLB2 CLB5
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Topics Genes linked to topics (#11 - 20 )
CLB6 CLN1 CLN2 CLN3 DBF2 GIS2 HEK2 IME2 NAB2 PCL1
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Topics Genes linked to topics (#21 - 29 )
PCL2 PCL9 PHO85 RAD23 RPN10 RUB1 SIC1 SKP1 SWI5
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