A matter of life or death: modeling DNA damage and repair in bacteria

Jens Karschau; Camila de Almeida; Morgiane C. Richard; Samantha Miller; Ian R. Booth; Celso Grebogi; Alessandro P. S. de Moura

doi:10.1016/j.bpj.2010.12.3713

A matter of life or death: modeling DNA damage and repair in bacteria

Jens Karschau, Camila de Almeida, Morgiane C. Richard, Samantha Miller, Ian R. Booth, Celso Grebogi, Alessandro P. S. de Moura

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	814-821
Number of pages	8
Journal	Biophysical Journal
Volume	100
Issue number	4
Early online date	15 Feb 2011
DOIs	https://doi.org/10.1016/j.bpj.2010.12.3713
Publication status	Published - 16 Feb 2011

Bibliographical note

A paid open access option is available for this journal.
Pre-prints on private websites only
Post-prints on author or institutional server only
Must link to publisher version
Authors version can be archived immediately following publication
If funding agency rules apply, authors may post their post print in PubMed Central 12 months after publication
Set phrase to accompany author's version
Publisher's version/PDF may be used
Publisher copyright and source must be acknowledged
Some articles can be made open access (Creative Commons Attribution Non-Commercial License) for a fee, and publisher will also submit to PubMed Central with no embargo
Please see Elsevier (Cell Press) for articles published in 2009 onwards

Keywords

Escherichia-coli-cells
double-strand breaks
methylglyoxal production
potassium channels
detoxification
inactivation
replication
activation
mechanisms
metabolite

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10.1016/j.bpj.2010.12.3713

Cite this

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title = "A matter of life or death: modeling DNA damage and repair in bacteria",

abstract = "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. ",

keywords = "Escherichia-coli-cells, double-strand breaks , methylglyoxal production, potassium channels, detoxification, inactivation, replication, activation, mechanisms, metabolite",

author = "Jens Karschau and {de Almeida}, Camila and Richard, {Morgiane C.} and Samantha Miller and Booth, {Ian R.} and Celso Grebogi and {de Moura}, {Alessandro P. S.}",

note = "A paid open access option is available for this journal. Pre-prints on private websites only Post-prints on author or institutional server only Must link to publisher version Authors version can be archived immediately following publication If funding agency rules apply, authors may post their post print in PubMed Central 12 months after publication Set phrase to accompany author's version Publisher's version/PDF may be used Publisher copyright and source must be acknowledged Some articles can be made open access (Creative Commons Attribution Non-Commercial License) for a fee, and publisher will also submit to PubMed Central with no embargo Please see Elsevier (Cell Press) for articles published in 2009 onwards ",

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T2 - modeling DNA damage and repair in bacteria

AU - Karschau, Jens

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AU - Richard, Morgiane C.

AU - Miller, Samantha

AU - Booth, Ian R.

AU - Grebogi, Celso

AU - de Moura, Alessandro P. S.

N1 - A paid open access option is available for this journal. Pre-prints on private websites only Post-prints on author or institutional server only Must link to publisher version Authors version can be archived immediately following publication If funding agency rules apply, authors may post their post print in PubMed Central 12 months after publication Set phrase to accompany author's version Publisher's version/PDF may be used Publisher copyright and source must be acknowledged Some articles can be made open access (Creative Commons Attribution Non-Commercial License) for a fee, and publisher will also submit to PubMed Central with no embargo Please see Elsevier (Cell Press) for articles published in 2009 onwards

PY - 2011/2/16

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N2 - 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.

AB - 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.

KW - Escherichia-coli-cells

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KW - potassium channels

KW - detoxification

KW - inactivation

KW - replication

KW - activation

KW - mechanisms

KW - metabolite

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JO - Biophysical Journal

JF - Biophysical Journal

IS - 4

ER -

A matter of life or death: modeling DNA damage and repair in bacteria

Abstract

Bibliographical note

Keywords

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