A mathematical model of a P53 oscillation network triggered by DNA damage

2010 ◽  
Vol 19 (4) ◽  
pp. 040506 ◽  
Author(s):  
Xia Jun-Feng ◽  
Jia Ya
Keyword(s):  
Mathematical Model ◽  
Dna Damage ◽  
Oscillation Network

scholarly journals The Contribution of p53 in the Dynamics of Cell Cycle Response to DNA Damage Interpreted by a Mathematical Model

Cell Cycle ◽  
2007 ◽  
Vol 6 (8) ◽  
pp. 943-950 ◽  
Author(s):  
Monica Lupi ◽  
Giada Matera ◽  
Claudia Natoli ◽  
Valentina Colombo ◽  
Paolo Ubezio
Keyword(s):  
Mathematical Model ◽  
Cell Cycle ◽  
Dna Damage

DNA fragment mass distributions following molecular recombination

1985 ◽  
Vol 17 (03) ◽  
pp. 496-513
Author(s):  
Thomas A. Darden ◽  
Michael A. Resnick
Keyword(s):  
Mathematical Model ◽  
Dna Damage ◽  
Sucrose Gradient ◽  
Repair Process ◽  
Recombinational Repair ◽  
Molecular Models ◽  
Fragment Mass ◽  
Mass Distributions ◽  
Dna Fragment ◽  
Gradient Measurements

A mathematical model for the process of recombinational repair of DNA damage is presented. Based on the model, a method is proposed for analyzing fragment mass distributions from experiments designed to detect recombinational repair in cells. The procedures developed can be used to analyze experiments involving sucrose-gradient measurements of mass distributions. The model also provides a framework for discussion of various molecular models of this repair process.

Modelling the comet assay

2009 ◽  
Vol 37 (4) ◽  
pp. 914-917 ◽  
Author(s):  
Darragh G. McArt ◽  
George McKerr ◽  
C. Vyvyan Howard ◽  
Kurt Saetzler ◽  
Gillian R. Wasson
Keyword(s):  
Mathematical Model ◽  
Dna Damage ◽  
Fluorescence Microscopy ◽  
Comet Assay ◽  
Gel Electrophoresis ◽  
Reliable Method ◽  
Track Record ◽  
Single Cell Gel Electrophoresis ◽  
Nutritional Studies ◽  
Electrophoresis Technique

The single-cell gel electrophoresis technique or comet assay is widely regarded as a quick and reliable method of analysing DNA damage in individual cells. It has a proven track record from the fields of biomonitoring to nutritional studies. The assay operates by subjecting cells that are fixed in agarose to high salt and detergent lysis, thus removing all the cellular content except the DNA. By relaxing the DNA in an alkaline buffer, strands containing breaks are released from supercoiling. Upon electrophoresis, these strands are pulled out into the agarose, forming a tail which, when stained with a fluorescent dye, can be analysed by fluorescence microscopy. The intensity of this tail reflects the amount of DNA damage sustained. Despite being such an established and widely used assay, there are still many aspects of the comet assay which are not fully understood. The present review looks at how the comet assay is being used, and highlights some of its limitations. The protocol itself varies among laboratories, so results from similar studies may vary. Given such discrepancies, it would be attractive to break the assay into components to generate a mathematical model to investigate specific parameters.

scholarly journals A predictive mathematical model of the DNA damage G2 checkpoint

2013 ◽  
Vol 320 ◽  
pp. 159-169 ◽  
Author(s):  
Kevin J. Kesseler ◽  
Michael L. Blinov ◽  
Timothy C. Elston ◽  
William K. Kaufmann ◽  
Dennis A. Simpson
Keyword(s):  
Mathematical Model ◽  
Dna Damage ◽  
G2 Checkpoint

scholarly journals A Mathematical Model for DNA Damage and Repair

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Philip S. Crooke ◽  
Fritz F. Parl
Keyword(s):  
Mathematical Model ◽  
Dna Damage ◽  
Dna Adducts ◽  
Excision Repair ◽  
Estrogen Metabolism ◽  
Enzymatic Reactions ◽  
Dna Damage And Repair ◽  
Base Excision ◽  
The Impact ◽  
Variant Enzyme

In cells, DNA repair has to keep up with DNA damage to maintain the integrity of the genome and prevent mutagenesis and carcinogenesis. While the importance of both DNA damage and repair is clear, the impact of imbalances between both processes has not been studied. In this paper, we created a combined mathematical model for the formation of DNA adducts from oxidative estrogen metabolism followed by base excision repair (BER) of these adducts. The model encompasses a set of differential equations representing the sequence of enzymatic reactions in both damage and repair pathways. By combining both pathways, we can simulate the overall process by starting from a given time-dependent concentration of 17β-estradiol (E2) and2′-deoxyguanosine, determine the extent of adduct formation and the correction by BER required to preserve the integrity of DNA. The model allows us to examine the effect of phenotypic and genotypic factors such as different concentrations of estrogen and variant enzyme haplotypes on the formation and repair of DNA adducts.

scholarly journals Mitigating Temozolomide Resistance in Glioblastoma via DNA Damage-Repair Inhibition

2019 ◽  
Author(s):  
Inmaculada C. Sorribes ◽  
Samuel K. Handelman ◽  
Harsh V. Jain
Keyword(s):  
Mathematical Model ◽  
Dna Damage ◽  
Treatment Efficacy ◽  
Mechanistic Model ◽  
Chemotherapy Resistance ◽  
Treatment Strategies ◽  
Cell Phenotype ◽  
Damage Repair ◽  
Cell Arrest ◽  
Dual Treatment

AbstractGlioblastomas are among the most lethal cancers, with a five year survival rate below 25%. Temozolomide is typically used in glioblastoma treatment; however, the enzymes APNG and MGMT efficiently mediate the repair of DNA damage caused by temozolomide, reducing treatment efficacy. Consequently, APNG and MGMT inhibition has been proposed as a way of overcoming chemotherapy resistance. Here, we develop a mechanistic mathematical model that explicitly incorporates the effect of chemotherapy on tumor cells, including the processes of DNA damage induction, cell arrest and DNA repair. Our model is carefully parameterized and validated, and then used to virtually recreate the response of heteroclonal glioblastoma to dual treatment with TMZ and inhibitors of APNG/MGMT. Using our mechanistic model, we identify four combination treatment strategies optimized by tumor cell phenotype, and isolate the strategy most likely to succeed in a pre-clinical and clinical setting. If confirmed in clinical trials, these strategies have the potential to offset chemotherapy resistance in glioblastoma patients, and improve overall survival.

DNA fragment mass distributions following molecular recombination

1985 ◽  
Vol 17 (3) ◽  
pp. 496-513 ◽  
Author(s):  
Thomas A. Darden ◽  
Michael A. Resnick
Keyword(s):  
Mathematical Model ◽  
Dna Damage ◽  
Sucrose Gradient ◽  
Repair Process ◽  
Recombinational Repair ◽  
Molecular Models ◽  
Fragment Mass ◽  
Mass Distributions ◽  
Dna Fragment ◽  
Gradient Measurements

A mathematical model for the process of recombinational repair of DNA damage is presented. Based on the model, a method is proposed for analyzing fragment mass distributions from experiments designed to detect recombinational repair in cells. The procedures developed can be used to analyze experiments involving sucrose-gradient measurements of mass distributions. The model also provides a framework for discussion of various molecular models of this repair process.

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