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Abstract

DNA within cells is subject to damage from various sources. Organisms have evolved a number of mechanisms to repair DNA damage. The activity of repair enzymes carries its own risk, however, because the repair of two nearby lesions may lead to the breakup of DNA and result in cell death. We propose a mathematical theory of the damage and repair process in the important scenario where lesions are caused in bursts. We use this model to show that there is an optimum level of repair enzymes within cells which optimises the cell's response to damage. This optimal level is explained as the best trade-off between fast repair and a low probability of causing double-stranded breaks. We derive our results analytically and test them using stochastic simulations, and compare our predictions with current biological knowledge. (C) 2011 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)39-43
Number of pages5
JournalJournal of Theoretical Biology
Volume292
Early online date19 Sep 2011
DOIs
Publication statusPublished - 7 Jan 2012

Fingerprint

DNA repair
DNA Repair
Repair
Optimality
DNA
Damage
Cell
cells
Enzymes
enzymes
DNA damage
DNA Damage
cell death
Cell Death
prediction
Breakup
organisms
Stochastic Simulation
Cell death
Burst

Keywords

  • DNA damage
  • DNA repair
  • stochastic modelling
  • nucleotide excision-repair
  • Escherichia-coli
  • mathematical-model
  • SOS response
  • damage
  • mechanisms
  • irradiation
  • radiation
  • survival

Cite this

Optimality in DNA repair. / Richard, Morgiane Carole; Fryett, Matthew; Miller, Samantha; Booth, Ian; Grebogi, Celso; Moura, Alessandro.

In: Journal of Theoretical Biology, Vol. 292, 07.01.2012, p. 39-43.

Research output: Contribution to journalArticle

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T1 - Optimality in DNA repair

AU - Richard, Morgiane Carole

AU - Fryett, Matthew

AU - Miller, Samantha

AU - Booth, Ian

AU - Grebogi, Celso

AU - Moura, Alessandro

PY - 2012/1/7

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N2 - DNA within cells is subject to damage from various sources. Organisms have evolved a number of mechanisms to repair DNA damage. The activity of repair enzymes carries its own risk, however, because the repair of two nearby lesions may lead to the breakup of DNA and result in cell death. We propose a mathematical theory of the damage and repair process in the important scenario where lesions are caused in bursts. We use this model to show that there is an optimum level of repair enzymes within cells which optimises the cell's response to damage. This optimal level is explained as the best trade-off between fast repair and a low probability of causing double-stranded breaks. We derive our results analytically and test them using stochastic simulations, and compare our predictions with current biological knowledge. (C) 2011 Elsevier Ltd. All rights reserved.

AB - DNA within cells is subject to damage from various sources. Organisms have evolved a number of mechanisms to repair DNA damage. The activity of repair enzymes carries its own risk, however, because the repair of two nearby lesions may lead to the breakup of DNA and result in cell death. We propose a mathematical theory of the damage and repair process in the important scenario where lesions are caused in bursts. We use this model to show that there is an optimum level of repair enzymes within cells which optimises the cell's response to damage. This optimal level is explained as the best trade-off between fast repair and a low probability of causing double-stranded breaks. We derive our results analytically and test them using stochastic simulations, and compare our predictions with current biological knowledge. (C) 2011 Elsevier Ltd. All rights reserved.

KW - DNA damage

KW - DNA repair

KW - stochastic modelling

KW - nucleotide excision-repair

KW - Escherichia-coli

KW - mathematical-model

KW - SOS response

KW - damage

KW - mechanisms

KW - irradiation

KW - radiation

KW - survival

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