title: Computational modelling of mitotic exit in budding yeast: the role of separase and Cdc14 endocycles.
abstract: The operating principles of complex regulatory networks are best understood with the help of mathematical modelling rather than by intuitive reasoning. Hereby, we study the dynamics of the mitotic exit (ME) control system in budding yeast by further developing the Queralt's model. A comprehensive systems view of the network regulating ME is provided based on classical experiments in the literature. In this picture, Cdc20-APC is a critical node controlling both cyclin (Clb2 and Clb5) and phosphatase (Cdc14) branches of the regulatory network. On the basis of experimental situations ranging from single to quintuple mutants, the kinetic parameters of the network are estimated. Numerical analysis of the model quantifies the dependence of ME control on the proteolytic and non-proteolytic functions of separase. We show that the requirement of the non-proteolytic function of separase for ME depends on cyclin-dependent kinase activity. The model is also used for the systematic analysis of the recently discovered Cdc14 endocycles. The significance of Cdc14 endocycles in eukaryotic cell cycle control is discussed as well.
authors.affiliation: Department of Biochemistry, Oxford Centre for Integrative Systems Biology, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: P K
authors.initials: PK
authors.lastname: Vinod
authors.forename: Paula
authors.initials: P
authors.lastname: Freire
authors.forename: Ahmed
authors.initials: A
authors.lastname: Rattani
authors.forename: Andrea
authors.initials: A
authors.lastname: Ciliberto
authors.forename: Frank
authors.initials: F
authors.lastname: Uhlmann
authors.forename: Bela
authors.initials: B
authors.lastname: Novak
mesh_terms: D001683:Biological Clocks / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D008954:Models, Biological; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D064247:Separase
chemical_list: C074860:CDC14 protein, S cerevisiae; D018797:Cell Cycle Proteins; D029701:Saccharomyces cerevisiae Proteins; D017027:Protein Tyrosine Phosphatases; D010450:Endopeptidases; C577986:ESP1 protein, S cerevisiae; D064247:Separase