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BIOMD0000000007 - Novak1997 - Cell Cycle

 

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Reference Publication
Publication ID: 9256450
Novak B, Tyson JJ.
Modeling the control of DNA replication in fission yeast.
Proc. Natl. Acad. Sci. U.S.A. 1997 Aug; 94(17): 9147-9152
Department of Agricultural Chemical Technology, Technical University of Budapest, 1521 Budapest, St. Gellert ter 4, Hungary.  [more]
Model
Original Model: BIOMD0000000007.xml.origin
Submitter: Nicolas Le Novère
Submission ID: MODEL6614787694
Submission Date: 13 Sep 2005 20:33:30 UTC
Last Modification Date: 26 Mar 2014 21:20:21 UTC
Creation Date: 15 Oct 2009 21:21:50 UTC
Encoders:  Nicolas Le Novère
   Bruce Shapiro
set #1
bqbiol:isHomologTo Reactome REACT_152
bqbiol:isVersionOf KEGG Pathway ko04110
Gene Ontology mitotic cell cycle
bqbiol:hasTaxon Taxonomy Schizosaccharomyces pombe
set #2
bqmodel:isDerivedFrom PubMed 10395816
Notes
Novak1997 - Cell Cycle

Modeling the control of DNA replication in fission yeast.

This model is described in the article:

Novak B., Tyson JJ.
Proc. Natl. Acad. Sci. U.S.A. 1997:94(17):9147-52

Abstract:

A central event in the eukaryotic cell cycle is the decision to commence DNA replication (S phase). Strict controls normally operate to prevent repeated rounds of DNA replication without intervening mitoses ("endoreplication") or initiation of mitosis before DNA is fully replicated ("mitotic catastrophe"). Some of the genetic interactions involved in these controls have recently been identified in yeast. From this evidence we propose a molecular mechanism of "Start" control in Schizosaccharomyces pombe. Using established principles of biochemical kinetics, we compare the properties of this model in detail with the observed behavior of various mutant strains of fission yeast: wee1(-) (size control at Start), cdc13Delta and rum1(OP) (endoreplication), and wee1(-) rum1Delta (rapid division cycles of diminishing cell size). We discuss essential features of the mechanism that are responsible for characteristic properties of Start control in fission yeast, to expose our proposal to crucial experimental tests.

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.

Model
Publication ID: 9256450 Submission Date: 13 Sep 2005 20:33:30 UTC Last Modification Date: 26 Mar 2014 21:20:21 UTC Creation Date: 15 Oct 2009 21:21:50 UTC
Mathematical expressions
Reactions
Cdc13_Cdc2 creation Cig2_Cdc2 creation Cdc2 phosphorylation binding of Rum1 with Cdc13_Cdc2
binding of Rum1 with Cdc13_P-Cdc2 Rum1 degradation in Rum1_Cdc13_Cdc2 Rum1 degradation in solution Rum1 degradation in Rum1_Cdc13_P-Cdc2
Rum1 degradation in Rum1_Cig2_Cdc2 Cdc13 degradation in Cdc13_Cdc2 Cdc13 degradation in Cdc13_P-Cdc2 Cig2 degradation in Cig2_Cdc2
Cdc13 degradation in Rum1_Cdc13_P-Cdc2 Cdc13 degradation in Rum1_Cdc13_Cdc2 Cig2 degradation in Rum1_Cig2_Cdc2 Binding of Rum1 to Cig2_Cdc2
UbE mediated degradation of Cdc13_Cdc2 in Rum1_Cdc13_Cdc2 UbE mediated degradation of Cdc13_Cdc2 in Rum1_Cdc13_P-Cdc2 Rum1 creation Rum1 degradation by SPF
IE production & degradation UbE production & degradation UbE2 production & degradation Wee1 production & degradation
Cdc25 production & degradation      
Rules
Rate Rule (variable: Mass) Assignment Rule (variable: BoundIntermediaryEnzyme) Assignment Rule (variable: BoundUbiquitinProtease1) Assignment Rule (variable: BoundUbiquitinProtease2)
Assignment Rule (variable: BoundWee1) Assignment Rule (variable: BoundCdc25) Assignment Rule (variable: TotalRum1) Assignment Rule (variable: TotalCdc13)
Assignment Rule (variable: TotalCig2) Assignment Rule (variable: k2) Assignment Rule (variable: k6) Assignment Rule (variable: kwee)
Assignment Rule (variable: k25) Assignment Rule (variable: M-phasePromotingFactor) Assignment Rule (variable: S-phasePromotingFactor)  
Events
S-Phase Start Cell Division    
Physical entities
Compartments Species
Cell ubiquitinProtease1 ubiquitinProtease2 Wee1
Cdc25 Cdc13_Cdc2 FreeRum1
Cig2_Cdc2 IntermediaryEnzyme Cdc13_P-Cdc2
Cig2_Cdc2_Rum1 Cdc13_Cdc2_Rum1 Cdc13_P-Cdc2_Rum1
S-phasePromotingFactor M-phasePromotingFactor BoundIntermediaryEnzyme
BoundUbiquitinProtease1 BoundUbiquitinProtease2 BoundWee1
BoundCdc25 TotalRum1 TotalCdc13
TotalCig2    
Global parameters
mu Mass k1 k2'
k3 k4 k5 k6'
k7 k7r k8 k8r
kc kcr ki kir
kp ku kur ku2
kur2 kw kwr V2
V2' V6 V6' V25
V25' Vw Vw' Kmc
Kmcr Kmi Kmir Kmp
Kmu Kmur Kmu2 Kmur2
Kmw Kmwr alpha beta
Cig1 k2 k6 kwee
k25      
Reactions (25)
 
 Cdc13_Cdc2 creation  → [Cdc13_Cdc2];  
 
 Cig2_Cdc2 creation  → [Cig2_Cdc2];  
 
 Cdc2 phosphorylation [Cdc13_Cdc2] ↔ [Cdc13_P-Cdc2];   {Wee1} , {Cdc25}
 
 binding of Rum1 with Cdc13_Cdc2 [Cdc13_Cdc2] + [FreeRum1] ↔ [Cdc13_Cdc2_Rum1];  
 
 binding of Rum1 with Cdc13_P-Cdc2 [Cdc13_P-Cdc2] + [FreeRum1] ↔ [Cdc13_P-Cdc2_Rum1];  
 
 Rum1 degradation in Rum1_Cdc13_Cdc2 [Cdc13_Cdc2_Rum1] → [Cdc13_Cdc2];  
 
 Rum1 degradation in solution [FreeRum1] → ;  
 
 Rum1 degradation in Rum1_Cdc13_P-Cdc2 [Cdc13_P-Cdc2_Rum1] → [Cdc13_P-Cdc2];  
 
 Rum1 degradation in Rum1_Cig2_Cdc2 [Cig2_Cdc2_Rum1] → [Cig2_Cdc2];  
 
 Cdc13 degradation in Cdc13_Cdc2 [Cdc13_Cdc2] → ;   {ubiquitinProtease1}
 
 Cdc13 degradation in Cdc13_P-Cdc2 [Cdc13_P-Cdc2] → ;   {ubiquitinProtease1}
 
 Cig2 degradation in Cig2_Cdc2 [Cig2_Cdc2] → ;   {ubiquitinProtease2}
 
 Cdc13 degradation in Rum1_Cdc13_P-Cdc2 [Cdc13_P-Cdc2_Rum1] → [FreeRum1];  
 
 Cdc13 degradation in Rum1_Cdc13_Cdc2 [Cdc13_Cdc2_Rum1] → [FreeRum1];  
 
 Cig2 degradation in Rum1_Cig2_Cdc2 [Cig2_Cdc2_Rum1] → [FreeRum1];  
 
 Binding of Rum1 to Cig2_Cdc2 [Cig2_Cdc2] + [FreeRum1] ↔ [Cig2_Cdc2_Rum1];  
 
 UbE mediated degradation of Cdc13_Cdc2 in Rum1_Cdc13_Cdc2 [Cdc13_Cdc2_Rum1] → [FreeRum1];   {ubiquitinProtease1}
 
 UbE mediated degradation of Cdc13_Cdc2 in Rum1_Cdc13_P-Cdc2 [Cdc13_P-Cdc2_Rum1] → [FreeRum1];   {ubiquitinProtease1}
 
 Rum1 creation  → [FreeRum1];  
 
 Rum1 degradation by SPF [FreeRum1] → ;   {S-phasePromotingFactor}
 
 IE production & degradation [BoundIntermediaryEnzyme] ↔ [IntermediaryEnzyme];   {M-phasePromotingFactor}
 
 UbE production & degradation [BoundUbiquitinProtease1] ↔ [ubiquitinProtease1];   {IntermediaryEnzyme}
 
 UbE2 production & degradation [BoundUbiquitinProtease2] ↔ [ubiquitinProtease2];   {M-phasePromotingFactor}
 
 Wee1 production & degradation [BoundWee1] ↔ [Wee1];   {M-phasePromotingFactor}
 
 Cdc25 production & degradation [BoundCdc25] ↔ [Cdc25];   {M-phasePromotingFactor}
 
Rules (15)
 
 Rate Rule (name: Mass) d [ Mass] / d t= Mass*mu
 
 Assignment Rule (name: IEB) BoundIntermediaryEnzyme = 1-IE
 
 Assignment Rule (name: UbEB) BoundUbiquitinProtease1 = 1-UbE
 
 Assignment Rule (name: UbE2B) BoundUbiquitinProtease2 = 1-UbE2
 
 Assignment Rule (name: Wee1B) BoundWee1 = 1-Wee1
 
 Assignment Rule (name: Cdc25B) BoundCdc25 = 1-Cdc25
 
 Assignment Rule (name: Rum1Total) TotalRum1 = G1R+G2R+PG2R+R
 
 Assignment Rule (name: Cdc13Total) TotalCdc13 = G2K+G2R+PG2+PG2R
 
 Assignment Rule (name: Cig2Total) TotalCig2 = G1K+G1R
 
 Assignment Rule (name: k2) k2 = UbE*V2+(1-UbE)*V2prime
 
 Assignment Rule (name: k6) k6 = UbE2*V6+(1-UbE2)*V6prime
 
 Assignment Rule (name: kwee) kwee = Vwprime*(1-Wee1)+Vw*Wee1
 
 Assignment Rule (name: k25) k25 = Cdc25*V25+(1-Cdc25)*V25prime
 
 Assignment Rule (name: MPF) M-phasePromotingFactor = G2K+beta*PG2
 
 Assignment Rule (name: SPF) S-phasePromotingFactor = Cig1+alpha*G1K+MPF
 
Events (2)
 
 S-Phase Start
kp = kp/2
 
 Cell Division
kp = 2*kp
Mass = Mass/2
 
 Cell Spatial dimensions: 3.0  Compartment size: 1.0  (Units: Predefined unit volume)
 
 ubiquitinProtease1
Compartment: Cell
Initial amount: 0.11
 
 ubiquitinProtease2
Compartment: Cell
Initial amount: 0.0
 
 Wee1
Compartment: Cell
Initial amount: 0.0
 
 Cdc25
Compartment: Cell
Initial amount: 0.0
 
 Cdc13_Cdc2
Compartment: Cell
Initial amount: 0.0
 
 FreeRum1
Compartment: Cell
Initial amount: 0.4
 
 Cig2_Cdc2
Compartment: Cell
Initial amount: 0.0
 
   IntermediaryEnzyme
Compartment: Cell
Initial amount: 0.0
 
 Cdc13_P-Cdc2
Compartment: Cell
Initial amount: 0.0
 
 Cig2_Cdc2_Rum1
Compartment: Cell
Initial amount: 0.0
 
 Cdc13_Cdc2_Rum1
Compartment: Cell
Initial amount: 0.0
 
 Cdc13_P-Cdc2_Rum1
Compartment: Cell
Initial amount: 0.0
 
  S-phasePromotingFactor
Compartment: Cell
Initial amount: 0.0
 
  M-phasePromotingFactor
Compartment: Cell
Initial amount: 0.0
 
   BoundIntermediaryEnzyme
Compartment: Cell
Initial amount: 0.0
 
  BoundUbiquitinProtease1
Compartment: Cell
Initial amount: 0.0
 
  BoundUbiquitinProtease2
Compartment: Cell
Initial amount: 0.0
 
  BoundWee1
Compartment: Cell
Initial amount: 0.0
 
  BoundCdc25
Compartment: Cell
Initial amount: 0.0
 
  TotalRum1
Compartment: Cell
 
  TotalCdc13
Compartment: Cell
 
  TotalCig2
Compartment: Cell
 
Global Parameters (49)
 
 mu
Value: 0.00495
Constant
 
   Mass
Value: 0.49
 
 k1
Value: 0.015
Constant
 
   k2'
Value: 0.05
Constant
 
 k3
Value: 0.09375
Constant
 
 k4
Value: 0.1875
Constant
 
 k5
Value: 0.00175
Constant
 
   k6'
Constant
 
 k7
Value: 100.0
Constant
 
 k7r
Value: 0.1
Constant
 
 k8
Value: 10.0
Constant
 
   k8r
Value: 0.1
Constant
 
   kc
Value: 1.0
Constant
 
   kcr
Value: 0.25
Constant
 
   ki
Value: 0.4
Constant
 
   kir
Value: 0.1
Constant
 
 kp
Value: 3.25
 
   ku
Value: 0.2
Constant
 
   kur
Value: 0.1
Constant
 
   ku2
Value: 1.0
Constant
 
   kur2
Value: 0.3
Constant
 
   kw
Value: 1.0
Constant
 
   kwr
Value: 0.25
Constant
 
   V2
Value: 0.25
Constant
 
   V2'
Value: 0.0075
Constant
 
   V6
Value: 7.5
Constant
 
   V6'
Value: 0.0375
Constant
 
   V25
Value: 0.5
Constant
 
   V25'
Value: 0.025
Constant
 
   Vw
Value: 0.35
Constant
 
   Vw'
Value: 0.035
Constant
 
   Kmc
Value: 0.1
Constant
 
   Kmcr
Value: 0.1
Constant
 
   Kmi
Value: 0.01
Constant
 
   Kmir
Value: 0.01
Constant
 
   Kmp
Value: 0.0010
Constant
 
   Kmu
Value: 0.01
Constant
 
   Kmur
Value: 0.01
Constant
 
   Kmu2
Value: 0.05
Constant
 
   Kmur2
Value: 0.05
Constant
 
   Kmw
Value: 0.1
Constant
 
   Kmwr
Value: 0.1
Constant
 
   alpha
Value: 0.25
Constant
 
   beta
Value: 0.05
Constant
 
   Cig1
Constant
 
  k2
Value: NaN
 
  k6
Value: NaN
 
  kwee
Value: NaN
 
  k25
Value: NaN
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000007

Curator's comment: (updated: 15 Oct 2009 16:25:07 PDT)

The figure corresponds to figure 2A of the original puplication. The plots in the paper were not reproduced by the model as such, but this is the best we were able to get from the parameters used in the paper without initial conditions. The model was simulated using Mathematica 6.0 - MathSBML 2.7.1.

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