A Matter of Life or Death: Modeling DNA Damage and Repair in Bacteria

DNA damage is a hazard all cells must face, and evolution has created a number of mechanisms to repair damaged bases in the chromosome. Paradoxically, many of these repair mechanisms can create double-strand breaks in the DNA molecule which are fatal to the cell. This indicates that the connection b...

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Bibliographic Details
Published in:Biophysical journal 2011-02, Vol.100 (4), p.814-821
Main Authors: Karschau, Jens, de Almeida, Camila, Richard, Morgiane C., Miller, Samantha, Booth, Ian R., Grebogi, Celso, de Moura, Alessandro P.S.
Format: Article
Language:English
Subjects:
Bacteria
Biological Systems and Multicellular Dynamics
Cells
Chromosomes
Computer Simulation
DNA Damage
DNA repair
DNA Repair - drug effects
Enzymes
Escherichia coli
Escherichia coli - cytology
Escherichia coli - drug effects
Escherichia coli - metabolism
Mathematical models
Microbial Viability - drug effects
Models, Biological
Pyruvaldehyde - toxicity
Stochastic Processes
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Summary:DNA damage is a hazard all cells must face, and evolution has created a number of mechanisms to repair damaged bases in the chromosome. Paradoxically, many of these repair mechanisms can create double-strand breaks in the DNA molecule which are fatal to the cell. This indicates that the connection between DNA repair and death is far from straightforward, and suggests that the repair mechanisms can be a double-edged sword. In this report, we formulate a mathematical model of the dynamics of DNA damage and repair, and we obtain analytical expressions for the death rate. We predict a counterintuitive relationship between survival and repair. We can discriminate between two phases: below a critical threshold in the number of repair enzymes, the half-life decreases with the number of repair enzymes, but becomes independent of the number of repair enzymes above the threshold. We are able to predict quantitatively the dependence of the death rate on the damage rate and other relevant parameters. We verify our analytical results by simulating the stochastic dynamics of DNA damage and repair. Finally, we also perform an experiment with Escherichia coli cells to test one of the predictions of our model.
ISSN:0006-3495
1542-0086
DOI:10.1016/j.bpj.2010.12.3713