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. Belov
Deputy 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
Induced DNA damages by ionizing radiation
DNA Damages
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Single-strand breaks
Base damages
Sugar damages
Double-strand breaks
Clustered DNA damages
DNA Repair
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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
Experimental data
Reaction’s code
Sequence of
Reactions
Output
Run
Results
1. Sequence of Reactions
2. Setting up reaction codes
dsDNA + RecBCD  Un-winded DNA * RecBCD complex
Un-winded DNA * RecBCD complex  Single Strand DNA tail
Single Strand DNA tail + RecA  Activated RecA enzyme
Activated RecA enzyme  Single Strand DNA tail + RecA
Activated RecA enzyme + H DNA  D-loop
D Loop  Holiday Junction
Holiday Junction  Repaired DNA
3. Parameters / Variables
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dsDNA
RecBCD
ssDNA tail
Complex
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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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N
t
t, s
t
t, s
Results
2. RecA enzyme concentration сhanges
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N
t, s
t, s
Results
3. D-Loop structure formation kinetics
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N
t, s
t, s
Results
4. Holiday Junction structure formation changes
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N
t, s
t, s
Results
5. Holiday Junction Vs. D-Loop
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N
t, s
t, s
Results
6. Repaired DNA formation kinetics
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N
t, s
t, s
Results
7. Repaired DNA Vs. DSB resolve
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N
t, s
t, s
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 radiations
in Escherichia coli bacteria.
Acknowledgments
• Dr. Oleg Belov, LRB, JINR
Thank You for Your Attention