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Optimality in DNA repair

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...

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Detalles Bibliográficos
Autores principales: Richard, Morgiane, Fryett, Matthew, Miller, Samantha, Booth, Ian, Grebogi, Celso, Moura, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4071444/
https://www.ncbi.nlm.nih.gov/pubmed/21945337
http://dx.doi.org/10.1016/j.jtbi.2011.08.024
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author Richard, Morgiane
Fryett, Matthew
Miller, Samantha
Booth, Ian
Grebogi, Celso
Moura, Alessandro
author_facet Richard, Morgiane
Fryett, Matthew
Miller, Samantha
Booth, Ian
Grebogi, Celso
Moura, Alessandro
author_sort Richard, Morgiane
collection PubMed
description 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.
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spelling pubmed-40714442014-07-07 Optimality in DNA repair Richard, Morgiane Fryett, Matthew Miller, Samantha Booth, Ian Grebogi, Celso Moura, Alessandro J Theor Biol Article 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. Elsevier 2012-01-07 /pmc/articles/PMC4071444/ /pubmed/21945337 http://dx.doi.org/10.1016/j.jtbi.2011.08.024 Text en © 2011 Elsevier Ltd. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Richard, Morgiane
Fryett, Matthew
Miller, Samantha
Booth, Ian
Grebogi, Celso
Moura, Alessandro
Optimality in DNA repair
title Optimality in DNA repair
title_full Optimality in DNA repair
title_fullStr Optimality in DNA repair
title_full_unstemmed Optimality in DNA repair
title_short Optimality in DNA repair
title_sort optimality in dna repair
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4071444/
https://www.ncbi.nlm.nih.gov/pubmed/21945337
http://dx.doi.org/10.1016/j.jtbi.2011.08.024
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