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BIOMD0000000475 - Amara2013 - PCNA ubiquitylation in the activation of PRR pathway

 

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Reference Publication
Publication ID: 23514624
Amara F, Colombo R, Cazzaniga P, Pescini D, Csikász-Nagy A, Falconi MM, Besozzi D, Plevani P.
In vivo and in silico analysis of PCNA ubiquitylation in the activation of the Post Replication Repair pathway in S. cerevisiae.
BMC Syst Biol 2013; 7: 24
Dipartimento di Bioscienze, Università degli Studi di Milano, Milano, Italy.  [more]
Model
Original Model: BIOMD0000000475.origin
Submitter: Paolo Cazzaniga
Submission ID: MODEL1211260000
Submission Date: 26 Nov 2012 15:21:14 UTC
Last Modification Date: 05 Mar 2014 16:56:10 UTC
Creation Date: 06 Sep 2013 16:57:28 UTC
Encoders:  Nick Juty
   Vijayalakshmi Chelliah
   Flavio Amara
   Marco Muzi Falconi
set #1
bqbiol:isVersionOf Gene Ontology postreplication repair
set #2
bqbiol:hasTaxon Taxonomy Saccharomyces cerevisiae
Notes
Mechanistic model of the Post-Replication Repair (PRR), the pathway involved in the bypass of DNA lesions induced by sunlight exposure and UV radiation. PRR acts through two different mechanisms, activated by mono- and poly-ubiquitylation of the DNA sliding clamp, called Proliferating Cell Nuclear Antigen (PCNA). This model has been defined according to the stochastic formulation of chemical kinetics [Gillespie DT, J Phys Chem 1977, 81(25):2340-2361], which requires to specify the set of molecular species occurring in the pathway and their respective interactions, formally described as a set of biochemical reactions. The volume considered for this system is 1.666667e-17L; this value can be used to convert the model into the deterministic formulation.
Model
Publication ID: 23514624 Submission Date: 26 Nov 2012 15:21:14 UTC Last Modification Date: 05 Mar 2014 16:56:10 UTC Creation Date: 06 Sep 2013 16:57:28 UTC
Mathematical expressions
Reactions
r01 r02 r03 r04
r05 r06 r07 r08
r09 r10 r11 r12
r13 r14 r15 r16
r17 r18 r19 r20
r21 r22 r23 r24
r25      
Rules
Assignment Rule (variable: PCNA_sum)      
Physical entities
Compartments Species
compartment L PCNA PCNAon
Rad18:Rad18 Rad18 Rad6
Rad6U U Rad18:Rad18:PCNAon
Rad18:Rad18:PCNAon:Rad6U Rad18:Rad18:PCNAonU PCNAonU
Rad5 Rad5:PCNAonU Ubc13U:Mms2
Ubc13U:Mms2:Rad5:PCNAonU Rad5:PCNAonU:U Ubc13:Mms2
PCNAonU:U Ubc13U:Mms2:Rad5:PCNAonU:U Rad5:PCNAonU:U:U
PCNAonU:U:U PCNAoff  
Global parameters
PCNA_sum      
Reactions (25)
 
 r01 [PCNA] + [L] → [PCNAon];   {PCNA} , {L}
 
 r02 2.0 × [Rad18] → [Rad18:Rad18];   {Rad18}
 
 r03 [Rad18:Rad18] → 2.0 × [Rad18];   {Rad18:Rad18}
 
 r04 [Rad6] + [U] → [Rad6U];   {Rad6} , {U}
 
 r05 [PCNAon] + [Rad18:Rad18] → [Rad18:Rad18:PCNAon];   {PCNAon} , {Rad18:Rad18}
 
 r06 [Rad18:Rad18:PCNAon] → [PCNAon] + [Rad18:Rad18];   {Rad18:Rad18:PCNAon}
 
 r07 [Rad6U] + [Rad18:Rad18:PCNAon] → [Rad18:Rad18:PCNAon:Rad6U];   {Rad6U} , {Rad18:Rad18:PCNAon}
 
 r08 [Rad18:Rad18:PCNAon:Rad6U] → [Rad6U] + [Rad18:Rad18:PCNAon];   {Rad18:Rad18:PCNAon:Rad6U}
 
 r09 [Rad18:Rad18:PCNAon:Rad6U] → [Rad6] + [Rad18:Rad18:PCNAonU];   {Rad18:Rad18:PCNAon:Rad6U}
 
 r10 [Rad18:Rad18:PCNAonU] → [Rad18:Rad18] + [PCNAonU];   {Rad18:Rad18:PCNAonU}
 
 r11 [U] + [Ubc13:Mms2] → [Ubc13U:Mms2];   {U} , {Ubc13:Mms2}
 
 r12 [PCNAonU] + [Rad5] → [Rad5:PCNAonU];   {PCNAonU} , {Rad5}
 
 r13 [Rad5:PCNAonU] → [PCNAonU] + [Rad5];   {Rad5:PCNAonU}
 
 r14 [Rad5:PCNAonU] + [Ubc13U:Mms2] → [Ubc13U:Mms2:Rad5:PCNAonU];   {Rad5:PCNAonU} , {Ubc13U:Mms2}
 
 r15 [Ubc13U:Mms2:Rad5:PCNAonU] → [Rad5:PCNAonU] + [Ubc13U:Mms2];   {Ubc13U:Mms2:Rad5:PCNAonU}
 
 r16 [Ubc13U:Mms2:Rad5:PCNAonU] → [Ubc13:Mms2] + [Rad5:PCNAonU:U];   {Ubc13U:Mms2:Rad5:PCNAonU}
 
 r17 [Rad5:PCNAonU:U] → [Rad5] + [PCNAonU:U];   {Rad5:PCNAonU:U}
 
 r18 [Rad5] + [PCNAonU:U] → [Rad5:PCNAonU:U];   {Rad5} , {PCNAonU:U}
 
 r19 [Ubc13U:Mms2] + [Rad5:PCNAonU:U] → [Ubc13U:Mms2:Rad5:PCNAonU:U];   {Ubc13U:Mms2} , {Rad5:PCNAonU:U}
 
 r20 [Ubc13U:Mms2:Rad5:PCNAonU:U] → [Ubc13U:Mms2] + [Rad5:PCNAonU:U];   {Ubc13U:Mms2:Rad5:PCNAonU:U}
 
 r21 [Ubc13U:Mms2:Rad5:PCNAonU:U] → [Ubc13:Mms2] + [Rad5:PCNAonU:U:U];   {Ubc13U:Mms2:Rad5:PCNAonU:U}
 
 r22 [Rad5:PCNAonU:U:U] → [Rad5] + [PCNAonU:U:U];   {Rad5:PCNAonU:U:U}
 
 r23 [PCNAonU] → [U] + [PCNAoff];   {PCNAonU}
 
 r24 [PCNAonU:U] → 2.0 × [U] + [PCNAoff];   {PCNAonU:U}
 
 r25 [PCNAonU:U:U] → 3.0 × [U] + [PCNAoff];   {PCNAonU:U:U}
 
Rules (1)
 
 Assignment Rule (name: parameter_1) PCNA_sum = species_12+species_19+species_22+species_11+species_14+species_17+species_21+species_20+species_16
 
 compartment Spatial dimensions: 3.0  Compartment size: 1.0
 
 L
Compartment: compartment
Initial concentration: 1001.0
 
 PCNA
Compartment: compartment
Initial concentration: 7480.0
 
 PCNAon
Compartment: compartment
Initial concentration: 0.0
 
 Rad18:Rad18
Compartment: compartment
Initial concentration: 0.0
 
 Rad18
Compartment: compartment
Initial concentration: 206.0
 
 Rad6
Compartment: compartment
Initial concentration: 194.0
 
 Rad6U
Compartment: compartment
Initial concentration: 0.0
 
 U
Compartment: compartment
Initial concentration: 8698.0
 
 Rad18:Rad18:PCNAon
Compartment: compartment
Initial concentration: 0.0
 
 Rad18:Rad18:PCNAon:Rad6U
Compartment: compartment
Initial concentration: 0.0
 
 Rad18:Rad18:PCNAonU
Compartment: compartment
Initial concentration: 0.0
 
 PCNAonU
Compartment: compartment
Initial concentration: 0.0
 
 Rad5
Compartment: compartment
Initial concentration: 1520.0
 
 Rad5:PCNAonU
Compartment: compartment
Initial concentration: 0.0
 
 Ubc13U:Mms2
Compartment: compartment
Initial concentration: 0.0
 
 Ubc13U:Mms2:Rad5:PCNAonU
Compartment: compartment
Initial concentration: 0.0
 
 Rad5:PCNAonU:U
Compartment: compartment
Initial concentration: 0.0
 
 Ubc13:Mms2
Compartment: compartment
Initial concentration: 193.0
 
 PCNAonU:U
Compartment: compartment
Initial concentration: 0.0
 
 Ubc13U:Mms2:Rad5:PCNAonU:U
Compartment: compartment
Initial concentration: 0.0
 
 Rad5:PCNAonU:U:U
Compartment: compartment
Initial concentration: 0.0
 
 PCNAonU:U:U
Compartment: compartment
Initial concentration: 0.0
 
 PCNAoff
Compartment: compartment
Initial concentration: 0.0
 
Global Parameters (1)
 
  PCNA_sum  
 
r01 (1)
 
   k1
Value: 1.5E-8
Constant
 
r02 (1)
 
   k1
Value: 0.01
Constant
 
r03 (1)
 
   k1
Value: 1000.0
Constant
 
r04 (1)
 
   k1
Value: 2.5E-7
Constant
 
r05 (1)
 
   k1
Value: 100000.0
Constant
 
r06 (1)
 
   k1
Value: 1000.0
Constant
 
r07 (1)
 
   k1
Value: 0.0351
Constant
 
r08 (1)
 
   k1
Value: 0.01
Constant
 
r09 (1)
 
   k1
Value: 0.01
Constant
 
r10 (1)
 
   k1
Value: 1.0
Constant
 
r11 (1)
 
   k1
Value: 100000.0
Constant
 
r12 (1)
 
   k1
Value: 5.0E-6
Constant
 
r13 (1)
 
   k1
Value: 0.005
Constant
 
r14 (1)
 
   k1
Value: 0.078
Constant
 
r15 (1)
 
   k1
Value: 1.0E-10
Constant
 
r16 (1)
 
   k1
Value: 0.05
Constant
 
r17 (1)
 
   k1
Value: 7.5E-6
Constant
 
r18 (1)
 
   k1
Value: 5.0E-6
Constant
 
r19 (1)
 
   k1
Value: 0.078
Constant
 
r20 (1)
 
   k1
Value: 1.0E-10
Constant
 
r21 (1)
 
   k1
Value: 0.005
Constant
 
r22 (1)
 
   k1
Value: 0.005
Constant
 
r23 (1)
 
   k1
Value: 3.0E-8
Constant
 
r24 (1)
 
   k1
Value: 8.0E-4
Constant
 
r25 (1)
 
   k1
Value: 0.005
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000475

Curator's comment: (updated: 06 Sep 2013 17:55:33 BST)

The paper has plots that correspond to different UV irradiation dose (5, 10, 50, 75J/m^2, etc.). The condition encoded in this model correspond to a UV irradiation of 5J/m^2, that should reproduce Figure 2B of the paper. Here, Figure 2B of the paper is reproduced. An assignment rule for PCNA_poly (i.e. PCNA_sum - the sum of every species in which PCNA isoforms (included complex) are involved) has been added to model to obtain the figure. The model time is in seconds and So, to run the simulation for 300mins, it has to be run for 18000(300x60) seconds.
The model was simulated using Copasi v4.10 (Build 55) and the plots were generated using Gnuplot.

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