Dataset Information

Amara2013 - PCNA ubiquitylation in the activation of PRR pathway

ABSTRACT: 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.

SUBMITTER: Paolo Cazzaniga

PROVIDER: BIOMD0000000475 | BioModels | 2013-09-06

REPOSITORIES: BioModels

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Publications

In vivo and in silico analysis of PCNA ubiquitylation in the activation of the Post Replication Repair pathway in S. cerevisiae.

Amara Flavio F Colombo Riccardo R Cazzaniga Paolo P Pescini Dario D Csikász-Nagy Attila A Falconi Marco Muzi MM Besozzi Daniela D Plevani Paolo P

BMC systems biology 20130320

<h4>Background</h4>The genome of living organisms is constantly exposed to several damaging agents that induce different types of DNA lesions, leading to cellular malfunctioning and onset of many diseases. To maintain genome stability, cells developed various repair and tolerance systems to counteract the effects of DNA damage. Here we focus on Post Replication Repair (PRR), the pathway involved in the bypass of DNA lesions induced by sunlight exposure and UV radiation. PRR acts through two diff ...[more]

PMID: 23514624

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Project description:Besozzi2012 - Oscillatory regimes in the Ras/cAMP/PKA pathway in S.cerevisiae Mechanistic model of the Ras/cAMP/PKA in yeast S.cerevisiae. The Ras/cAMP/PKA pathway plays a major role in the regulation of metabolism, stress resistance and cell cycle progress and is tightly regulated by multiple feedback loops, exerted by the protein kinase A (PKA). This model investigates the dynamics of the second messenger cAMP on Ras/cAMP/PKA pathway, to determine the effects of the feedback mechanisms on establising stable oscillatory regimes. The model has been defined according to the stochastic formulation of chemical kinetics [Gillespie DT, 1977] , 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 30fL; this value can be used to convert the model into the deterministic formulation. This model is described in the article: The role of feedback control mechanisms on the establishment of oscillatory regimes in the Ras/cAMP/PKA pathway in S. cerevisiae. Besozzi D, Cazzaniga P, Pescini D, Mauri G, Colombo S, Martegani E. EURASIP J Bioinform Syst Biol. 2012 Jul 20;2012(1):10. Abstract: In the yeast Saccharomyces cerevisiae, the Ras/cAMP/PKA pathway is involved in the regulation of cell growth and proliferation in response to nutritional sensing and stress conditions. The pathway is tightly regulated by multiple feedback loops, exerted by the protein kinase A (PKA) on a few pivotal components of the pathway. In this article, we investigate the dynamics of the second messenger cAMP by performing stochastic simulations and parameter sweep analysis of a mechanistic model of the Ras/cAMP/PKA pathway, to determine the effects that the modulation of these feedback mechanisms has on the establishment of stable oscillatory regimes. In particular, we start by studying the role of phosphodiesterases, the enzymes that catalyze the degradation of cAMP, which represent the major negative feedback in this pathway. Then, we show the results on cAMP oscillations when perturbing the amount of protein Cdc25 coupled with the alteration of the intracellular ratio of the guanine nucleotides (GTP/GDP), which are known to regulate the switch of the GTPase Ras protein. This multi-level regulation of the amplitude and frequency of oscillations in the Ras/cAMP/PKA pathway might act as a fine tuning mechanism for the downstream targets of PKA, as also recently evidenced by some experimental investigations on the nucleocytoplasmic shuttling of the transcription factor Msn2 in yeast cells. This model is hosted on BioModels Database and identified by: BIOMD0000000478 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . 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.

Dataset Information

Amara2013 - PCNA ubiquitylation in the activation of PRR pathway

Publications

In vivo and in silico analysis of PCNA ubiquitylation in the activation of the Post Replication Repair pathway in S. cerevisiae.

Similar Datasets

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