Mathematical modeling of recombination repair mechanism for double strand DNA breaks in Escherichia coli bacterial cells
Alaa Mohamed
Researcher Assistant,Nano Science and Technology Center, Nile University, Cairo,Egypt. Under the supervision of:
Dr. Oleg V. BelovDeputy Head of the Radiobiology Department,Laboratory of Radiation Biology,Joint Institute for Nuclear Research
The Project of LRB
Mathematical modeling of repair systems in living organisms
Dr. Oleg Belov, Laboratory of Radiation Biology
UV irradiation and Mutagenesis
The Project’s aim
Ionizing radiation Ionizing radiation
Induced DNA damages by ionizing radiation
DNA Damages • Single-strand breaks• Base damages• Sugar damages • Double-strand breaks• Clustered DNA damages
DNA Repair
• Base excision repair• Nucleotide excision repair• Mismatch repair• Recombination repair • SOS repair
The Project
We quantitatively modeled the recombination repair mechanism for DNA double strands breaks, induced by ionization radiation, in
Escherichia coli bacterial cells
Steps for building up the model
1. Sequence of Reactions
2. Setting up reaction codes
3. Parameters / Variables
• dsDNA• RecBCD• ssDNA tail • Complex
• RecA• D-Loop• Holiday Junction • Repaired DNA
4. Output
• All reactions were simulated using Mathematica software, using two approaches: 1. Stochastic approach 2. Deterministic approach
• Outputs we obtained, characterized DNA repair steps as well as enzymes’ concentration changes.
Results
1. RecBCD complex concentration changes
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2. RecA enzyme concentration сhangesNN
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3. D-Loop structure formation kinetics
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4. Holiday Junction structure formation changes
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5. Holiday Junction Vs. D-LoopNN
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6. Repaired DNA formation kineticsNN
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7. Repaired DNA Vs. DSB resolveNN
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Conclusion • Determined the key processes making the main
contribution to the functioning of DNA recombination repair system
• Developed a phenomenological model for DNA recombination repair system
• Constructed a mathematical model for the DNA recombination repair system using the deterministic and stochastic approaches
• Obtained and analyzed solutions for the proposed model
Future tasks
• Development of mathematical models for other DNA repair systems.
• Development of mutagenesis model for damages induced by ionization radiationsin Escherichia coli bacteria.
Acknowledgments
• Dr. Oleg Belov, LRB, JINR
Thank You for Your Attention