mathematical modeling of recombination repair mechanism for double strand dna breaks in escherichia...

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