Aguda1999 - G2 DNA damage checkpoint

  public model
Model Identifier
BIOMD0000000704
Short description
Format
SBML (L2V4)
Related Publication
  • A quantitative analysis of the kinetics of the G(2) DNA damage checkpoint system.
  • Aguda BD
  • Proceedings of the National Academy of Sciences of the United States of America , 9/ 1999 , Volume 96 , Issue 20 , pages: 11352-11357 , PubMed ID: 10500180
  • Department of Chemistry, Laurentian University, Sudbury, Ontario, Canada P3E 2C6. daguda@nickel.laurentian.ca
  • A detailed model of the G(2) DNA damage checkpoint (G2DDC) system is presented that includes complex regulatory networks of the mitotic kinase Cdc2, phosphatase Cdc25, Wee1 kinase, and damage signal transduction pathways involving Chk1 and p53. Assumptions on the kinetic equations of the G2DDC are made, and computer simulations are carried out to demonstrate how the various subsystems operate to delay or arrest cell cycle progression. The detailed model could be used to explain various experiments relevant to G2DDC reported recently, including the nuclear export of 14-3-3-bound Cdc25, the down-regulation of cyclin B1 expression by p53, the effect of Chk1 and p53 on Cdc25 levels, and Wee1 degradation. It also is shown that, under certain conditions, p53 is necessary to sustain a G(2) arrest.
Contributors
Submitter of the first revision: Lukas Endler
Submitter of this revision: administrator
Modellers: administrator, Lukas Endler

Metadata information

is (2 statements)
BioModels Database MODEL6960055446
BioModels Database BIOMD0000000704

isDescribedBy (2 statements)
PubMed 10500180
PubMed 10500180

hasTaxon (1 statement)
Taxonomy Vertebrata

hasPart (1 statement)
Gene Ontology G2 DNA damage checkpoint

hasProperty (1 statement)
Mathematical Modelling Ontology Ordinary differential equation model

Curation status
Curated
Modelling approach(es)
ordinary differential equation model
Tags

Connected external resources

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Name Description Size Actions

Model files
BIOMD0000000704_url.xml SBML L2V4 representation of Aguda1999 - G2 DNA damage checkpoint 140.65 KB Preview | Download

Additional files
BIOMD0000000704-biopax2.owl Auto-generated BioPAX (Level 2) 43.95 KB Preview | Download
BIOMD0000000704.m Auto-generated Octave file 14.29 KB Preview | Download
BIOMD0000000704.png Auto-generated Reaction graph (PNG) 257.82 KB Preview | Download
BIOMD0000000704.sci Auto-generated Scilab file 154.00 Bytes Preview | Download
BIOMD0000000704.svg Auto-generated Reaction graph (SVG) 78.32 KB Preview | Download
BIOMD0000000704.vcml Auto-generated VCML file 161.14 KB Preview | Download
BIOMD0000000704.xpp Auto-generated XPP file 11.14 KB Preview | Download
BIOMD0000000704_urn.xml Auto-generated SBML file with URNs 140.13 KB Preview | Download
Figure8.cps Copasi file for reproducing figure 8 in the reference publication. 160.98 KB Preview | Download
figure8.sedml SEDML file to reproduce Figure 8 in the reference publication 2.78 KB Preview | Download

  • Model originally submitted by : Lukas Endler
  • Submitted: Mar 23, 2009 10:03:26 AM
  • Last Modified: May 29, 2018 6:22:26 PM
Revisions
  • Version: 3 public model Download this version
    • Submitted on: May 29, 2018 6:22:26 PM
    • Submitted by: administrator
    • With comment: Model of the reference publication with annotations and explicit names for species and reactions
  • Version: 2 public model Download this version
    • Submitted on: Jul 4, 2011 4:56:16 PM
    • Submitted by: Lukas Endler
    • With comment: Current version of Aguda1999_G2_Damage_Checkpoint
  • Version: 1 public model Download this version
    • Submitted on: Mar 23, 2009 10:03:26 AM
    • Submitted by: Lukas Endler
    • With comment: Original import of Aguda 1999 G2 damage checkpoint

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
Cdc25 inactive

M-phase inducer phosphatase 1 ; Inactivity 		1.0E-6 mmol
p21

Cyclin-dependent kinase inhibitor 1 		0.0 mmol
MPF

Cyclin-dependent kinase 1 ; Active ; G2/mitotic-specific cyclin-B1 ; protein-containing complex 		1.0E-8 mmol
preMPF

G2/mitotic-specific cyclin-B1 ; Inactivity ; Cyclin-dependent kinase 1 ; protein-containing complex 		1.0E-6 mmol
Cdc25 active total

M-phase inducer phosphatase 1 ; Active 		1.0E-6 mmol
Cdc25Ps216 inactive

M-phase inducer phosphatase 1 ; Inactivity ; phosphorylated 		2.0E-5 mmol
Chk1

Serine/threonine-protein kinase Chk1 		0.999999 mmol
protein 14 3 3

14-3-3 protein sigma 		2.0 mmol
Reactions
Reactions Rate Parameters
Cdc25_active => Cdc25_inactive nucleus*k7_0*Cdc25_active k7_0 = 0.01
=> p21 nucleus*k21 k21 = 0.01
preMPF => MPF; Cdc25_active, Cdc25Ps216_active nucleus*(k9*(Cdc25_active+Cdc25Ps216_active)*preMPF+k9_0*preMPF) k9_0 = 0.0; k9 = 1.0
=> preMPF; p53 nucleus*k14/(1+k14_0*p53) k14_0 = 1.0; k14 = 5.0E-4
p21 + MPF => p21_MPF nucleus*k23*p21*MPF k23 = 0.1
Cdc25_active_total = Cdc25_active+Cdc25Ps216_active [] []
protein_14_3_3 + Cdc25Ps216_inactive => Cdc25Ps216_14_3_3_inactive nucleus*k3*protein_14_3_3*Cdc25Ps216_inactive k3 = 100.0
p21 => nucleus*k22*p21 k22 = 0.1
Chk1 => Chk1P; Rad3_ATM nucleus*k1*Chk1*Rad3_ATM k1 = 1.0
=> protein_14_3_3 nucleus*k13 k13 = 1.0
Curator's comment:
(added: 29 May 2018, 18:28:36, updated: 29 May 2018, 18:28:36)
Figure 8 of the reference publication has been reproduced using Copasi 4.23 (Build 184)