title: Optimality in DNA repair.
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.
authors.affiliation: Institute of Complex Systems and Mathematical Biology, King's College, University of Aberdeen, Aberdeen, UK.
authors.forename: Morgiane
authors.initials: M
authors.lastname: Richard
authors.forename: Matthew
authors.initials: M
authors.lastname: Fryett
authors.forename: Samantha
authors.initials: S
authors.lastname: Miller
authors.forename: Ian
authors.initials: I
authors.lastname: Booth
authors.forename: Celso
authors.initials: C
authors.lastname: Grebogi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moura
mesh_terms: D000818:Animals; D016923:Cell Death / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000502:physiology; D008957:Models, Genetic; D013269:Stochastic Processes
chemical_list: D045643:DNA Repair Enzymes