Adaptation to DNA damage as a bet-hedging mechanism in a fluctuating environment
| Autor: | Pierre Roux, Delphine Salort, Zhou Xu |
|---|---|
| Přispěvatelé: | HAL-SU, Gestionnaire, Biologie Computationnelle et Quantitative = Laboratory of Computational and Quantitative Biology (LCQB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Mathématiques d'Orsay (LMO), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Genome instability
Cell division DNA damage Science [SDV]Life Sciences [q-bio] theoretical biology adaptation Biology 03 medical and health sciences 0302 clinical medicine applied mathematics mathematical modelling bet-hedging Research Articles 030304 developmental biology 0303 health sciences Mechanism (biology) biomathematics mathematical modelling Cell cycle G2-M DNA damage checkpoint Hedgehog signaling pathway Cell biology [SDV] Life Sciences [q-bio] repair Adaptation heterogeneity 030217 neurology & neurosurgery Mathematics |
| Zdroj: | Royal Society Open Science Royal Society Open Science, 2021, 8 (8), pp.210460. ⟨10.1098/rsos.210460⟩ Royal Society Open Science, The Royal Society, 2021, 8 (8), pp.210460. ⟨10.1098/rsos.210460⟩ Royal Society Open Science, Vol 8, Iss 8 (2021) |
| ISSN: | 2054-5703 |
| Popis: | In response to DNA damage, efficient repair is essential for cell survival and genome integrity. In eukaryotes, the DNA damage checkpoint is a signalling pathway that coordinates this response and arrests the cell cycle to provide time for repair. However, when repair fails or when the damage is not repairable, cells can eventually bypass the DNA damage checkpoint and undergo cell division despite persistent damage, a process called adaptation to DNA damage. Interestingly, adaptation occurs with a delayed timing compared to repair and shows a large variation in time, two properties that may provide a survival advantage at the population level without interfering with repair. Here, we explore this idea by mathematically modelling cell survival in response to DNA damage and focusing on adaptation parameters. We find that the delayed adaptation timing indeed maximizes survival, but its heterogeneity is beneficial only in a fluctuating damage-inducing environment. Finally, we show that adaptation does not only contribute to survival but also to genome instability and mutations, which might represent another criterion for its selection through-out evolution. Overall, we propose that adaptation can act as a bet-hedging mechanism for cell survival in response to DNA damage. |
| Databáze: | OpenAIRE |
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