Dataset Information

Ciliberto2003_Morphogenesis_Checkpoint

ABSTRACT: This a model from the article: Mathematical model of the morphogenesis checkpoint in budding yeast. Ciliberto A, Novak B, Tyson JJ J. Cell Biol. [2003 Dec; Volume: 163 (Issue: 6 )] Page info: 1243-54 14691135 , Abstract: The morphogenesis checkpoint in budding yeast delays progression through the cell cycle in response to stimuli that prevent bud formation. Central to the checkpoint mechanism is Swe1 kinase: normally inactive, its activation halts cell cycle progression in G2. We propose a molecular network for Swe1 control, based on published observations of budding yeast and analogous control signals in fission yeast. The proposed Swe1 network is merged with a model of cyclin-dependent kinase regulation, converted into a set of differential equations and studied by numerical simulation. The simulations accurately reproduce the phenotypes of a dozen checkpoint mutants. Among other predictions, the model attributes a new role to Hsl1, a kinase known to play a role in Swe1 degradation: Hsl1 must also be indirectly responsible for potent inhibition of Swe1 activity. The model supports the idea that the morphogenesis checkpoint, like other checkpoints, raises the cell size threshold for progression from one phase of the cell cycle to the next. The model reproduces Fig 3 of the paper. This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. For more information see the terms of use . To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

SUBMITTER: Harish Dharuri

PROVIDER: BIOMD0000000297 | BioModels | 2024-09-02

REPOSITORIES: BioModels

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			Action	DRS
	BIOMD0000000297?filename=BIOMD0000000297-biopax2.owl	Owl
	BIOMD0000000297?filename=BIOMD0000000297-biopax3.owl	Owl
	BIOMD0000000297?filename=BIOMD0000000297.m	Other
	BIOMD0000000297?filename=BIOMD0000000297.pdf	Pdf
	BIOMD0000000297?filename=BIOMD0000000297.png	Other

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Publications

Mathematical model of the morphogenesis checkpoint in budding yeast.

Ciliberto Andrea A Novak Bela B Tyson John J JJ

The Journal of cell biology 20031201 6

The morphogenesis checkpoint in budding yeast delays progression through the cell cycle in response to stimuli that prevent bud formation. Central to the checkpoint mechanism is Swe1 kinase: normally inactive, its activation halts cell cycle progression in G2. We propose a molecular network for Swe1 control, based on published observations of budding yeast and analogous control signals in fission yeast. The proposed Swe1 network is merged with a model of cyclin-dependent kinase regulation, conve ...[more]

PMID: 14691135

Similar Datasets

Project description:This a model from the article: Mathematical model of the morphogenesis checkpoint in budding yeast. Ciliberto A, Novak B, Tyson JJ. J Cell Biol 2003 Dec 22;163(6):1243-54 14691135 , Abstract: The morphogenesis checkpoint in budding yeast delays progression through the cell cycle in response to stimuli that prevent bud formation. Central to the checkpoint mechanism is Swe1 kinase: normally inactive, its activation halts cell cycle progression in G2. We propose a molecular network for Swe1 control, based on published observations of budding yeast and analogous control signals in fission yeast. The proposed Swe1 network is merged with a model of cyclin-dependent kinase regulation, converted into a set of differential equations and studied by numerical simulation. The simulations accurately reproduce the phenotypes of a dozen checkpoint mutants. Among other predictions, the model attributes a new role to Hsl1, a kinase known to play a role in Swe1 degradation: Hsl1 must also be indirectly responsible for potent inhibition of Swe1 activity. The model supports the idea that the morphogenesis checkpoint, like other checkpoints, raises the cell size threshold for progression from one phase of the cell cycle to the next. This model was taken from the CellML repository and automatically converted to SBML. The original model was: Ciliberto A, Novak B, Tyson JJ. (2003) - version03 The original CellML model was created by: Lloyd, Catherine, May c.lloyd@aukland.ac.nz The University of Auckland The Bioengineering Institute This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Project description:In budding yeast, DNA lesions and stalled replication forks are sensed by the apical checkpoint kinase Mec1/ATR, which leads to the downstream activation of the effector kinase Rad53/CHK1. This activation depends on Rad9 and Mrc1, two checkpoint mediators that integrate the nature of the challenge in different phases of the cell cycle. Rad9 mediates the activation of the DNA damage checkpoint throughout the cell cycle, while the function of Mrc1 is restricted to the S phase of the cell cycle, when it travels with the replication fork and activates the DNA replication checkpoint in response to a variety of replication impediments. In this scenario, the role of Rad9 in S phase has been largely disregarded since the discovery of Mrc1, because Rad9 is dispensable for the timely activation of Rad53 in response to the drug hydroxyurea, which halts forks, and is only recruited to those stalled forks when Mrc1 is absent. Thus, Rad9 is simply believed to act as a backup pathway for Mrc1 during replication. We have re-evaluated the role of Rad9 when DNA damage arises during replication and characterized its functional interplay with Mrc1. To this end, we have used genome-wide approaches, single-molecule analysis, pulsed-field and 2D gel electrophoresis, as well as a careful combination of different replication-challenging drugs. We have found that both Mrc1 and Rad9 play distinct but complementary functions in the replication stress response during S phase, for they coordinate the early and late functions of Rad53, respectively. While Mrc1 is responsible for the fast activation of Rad53 in response to fork-halting drugs in order to repress late origins, Rad9 maintains Rad53 in an active state during prolonged fork arrest and is necessary to sustain this response for long periods. Remarkably, we also have found that Rad9 possesses the unprecedented activity of slowing down replication fork progression in response to DNA damage. This work thus restores the legitimate role of Rad9 as a central actor in the maintenance of genome integrity during replication. This has important implications for our understanding of the management of the checkpoint during perturbed replication in human cells, for Rad9 has three orthologues, 53BP1, BRCA1 and MDC1, whose contribution to this aspect of genome integrity remains largely unexplored.