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BIOMD0000000216 - Hong2009_CircadianClock

 

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Reference Publication
Publication ID: 19424508
Hong CI, Zámborszky J, Csikász-Nagy A.
Minimum criteria for DNA damage-induced phase advances in circadian rhythms.
PLoS Comput. Biol. 2009 May; 5(5): e1000384
Department of Genetics, Dartmouth Medical School, Hanover, New Hampshire, USA.  [more]
Model
Original Model: BIOMD0000000216.origin
Submitter: Judit Zamborszky
Submission ID: MODEL7984093336
Submission Date: 15 Jun 2009 10:55:47 UTC
Last Modification Date: 25 Feb 2015 13:15:34 UTC
Creation Date: 03 Apr 2009 11:51:42 UTC
Encoders:  Vijayalakshmi Chelliah
   Christian Hong
   Judit Zamborszky
set #1
bqmodel:isDerivedFrom PubMed 18057329
set #2
bqbiol:isVersionOf KEGG Pathway Circadian rhythm
Gene Ontology regulation of circadian rhythm
bqbiol:hasTaxon Taxonomy Mammalia
Notes

This a model from the article:
Minimum criteria for DNA damage-induced phase advances in circadian rhythms.
Hong CI, Zámborszky J, Csikász-Nagy A. PLoS Comput Biol. 2009 May;5(5):e1000384. 19424508,
Abstract:
Robust oscillatory behaviors are common features of circadian and cell cycle rhythms. These cyclic processes, however, behave distinctively in terms of their periods and phases in response to external influences such as light, temperature, nutrients, etc. Nevertheless, several links have been found between these two oscillators. Cell division cycles gated by the circadian clock have been observed since the late 1950s. On the other hand, ionizing radiation (IR) treatments cause cells to undergo a DNA damage response, which leads to phase shifts (mostly advances) in circadian rhythms. Circadian gating of the cell cycle can be attributed to the cell cycle inhibitor kinase Wee1 (which is regulated by the heterodimeric circadian clock transcription factor, BMAL1/CLK), and possibly in conjunction with other cell cycle components that are known to be regulated by the circadian clock (i.e., c-Myc and cyclin D1). It has also been shown that DNA damage-induced activation of the cell cycle regulator, Chk2, leads to phosphorylation and destruction of a circadian clock component (i.e., PER1 in Mus or FRQ in Neurospora crassa). However, the molecular mechanism underlying how DNA damage causes predominantly phase advances in the circadian clock remains unknown. In order to address this question, we employ mathematical modeling to simulate different phase response curves (PRCs) from either dexamethasone (Dex) or IR treatment experiments. Dex is known to synchronize circadian rhythms in cell culture and may generate both phase advances and delays. We observe unique phase responses with minimum delays of the circadian clock upon DNA damage when two criteria are met: (1) existence of an autocatalytic positive feedback mechanism in addition to the time-delayed negative feedback loop in the clock system and (2) Chk2-dependent phosphorylation and degradation of PERs that are not bound to BMAL1/CLK.

The original xpp file of the model is available as a supplement of the article (Text S1).

This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2010 The BioModels Team.
For more information see the terms of use.
To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.

Model
Publication ID: 19424508 Submission Date: 15 Jun 2009 10:55:47 UTC Last Modification Date: 25 Feb 2015 13:15:34 UTC Creation Date: 03 Apr 2009 11:51:42 UTC
Mathematical expressions
Reactions
r1 r2 r3 r4
r5 r6 r7 r8
r9 r10 r11 r12
r13 r14 r15 r16
r17      
Rules
Assignment Rule (variable: CPtot)      
Physical entities
Compartments Species
system M TF CP
CP2 IC CPtot
Global parameters
Dex kms n J
kmd kcps kcpd ka
kd kp1 Jp chk2
kicd kcp2d kica chk2c
kp2 TFtot    
Reactions (17)
 
 r1  → [M];  
 
 r2  → [M];   {TF}
 
 r3 [M] → ;  
 
 r4  → [CP];   {M}
 
 r5 [CP] → ;  
 
 r6 2.0 × [CP] → [CP2];  
 
 r7 [CP2] → 2.0 × [CP];  
 
 r8 [CP] → ;   {CP2} , {IC}
 
 r9 [CP] → ;  
 
 r10 [IC] → [CP2] + [TF];  
 
 r11 [CP2] → ;  
 
 r12 [CP2] + [TF] → [IC];  
 
 r13 [CP2] → ;   {CP} , {IC}
 
 r14 [CP2] → ;  
 
 r15 [IC] → [TF];  
 
 r16 [IC] → [TF];  
 
 r17 [IC] → [TF];   {CP2} , {CP}
 
Rules (1)
 
 Assignment Rule (name: CPtot) CPtot = CP+2*CP2+2*IC
 
Functions (6)
 
 function_4_r1 lambda(Dex, system, Dex/system)
 
 function_4_r8 lambda(CP, CP2, IC, Jp, kp1, system, kp1*CP/(Jp+CP+2*CP2+2*IC)/system)
 
 function_4_r2 lambda(J, TF, kms, n, system, kms*TF^n/(J^n+TF^n)/system)
 
 function_4_r17 lambda(CP, CP2, IC, Jp, kp2, system, kp2*IC/(Jp+CP+2*CP2+2*IC)/system)
 
 function_4_r13 lambda(CP, CP2, IC, Jp, kp2, system, kp2*CP2/(Jp+CP+2*CP2+2*IC)/system)
 
 Rate Law for r4 lambda(kcps, M, kcps*M)
 
 system Spatial dimensions: 3.0  Compartment size: 1.0
 
 M
Compartment: system
Initial concentration: 1.4
 
 TF
Compartment: system
Initial concentration: 0.13
 
 CP
Compartment: system
Initial concentration: 0.037
 
 CP2
Compartment: system
Initial concentration: 0.046
 
 IC
Compartment: system
Initial concentration: 0.37
 
   CPtot
Compartment: system
 
Global Parameters (18)
 
 Dex
Constant
 
   kms
Value: 1.0
Constant
 
   n
Value: 2.0
Constant
 
   J
Value: 0.3
Constant
 
   kmd
Value: 0.1
Constant
 
   kcps
Value: 0.5
Constant
 
   kcpd
Value: 0.525
Constant
 
   ka
Value: 100.0
Constant
 
   kd
Value: 0.01
Constant
 
   kp1
Value: 10.0
Constant
 
   Jp
Value: 0.05
Constant
 
   chk2
Constant
 
   kicd
Value: 0.01
Constant
 
   kcp2d
Value: 0.0525
Constant
 
   kica
Value: 20.0
Constant
 
   chk2c
Constant
 
   kp2
Value: 0.1
Constant
 
 TFtot
Value: 1.0
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000216

Curator's comment: (updated: 15 Jun 2009 11:55:29 BST)

The figure 2C of the reference publication is reproduced. To reproduce figure 2C, the following initial conditions were used (as per the authors suggestion). This is different from that of the model.
M=1.35; CP=0.039; CP2=0.088; TF=0.06; IC=0.44 (TFtot=0.5 & IC=TFtot-TF).
The model was simulation and run using Copasi v4.5

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