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Investigating mechanisms of endogenous, systems-level coordination in stress adaptation and homeostasis

  • Author(s): Bonny, Alain
  • Advisor(s): El-Samad, Hana
  • et al.
Abstract

Cells routinely deploy a spectrum of specialized counter-measures to deal with stress. However, a near constant feature of response to stress is a down regulation or arrest of the cell cycle. It has been widely assumed that this cell cycle modulation facilitates a faster cellular adaptation, a hypothesis that has been posited but still awaits strong support. Here, we used the \textit{S. cerevisiae} hyperosmotic shock response as a model system to pursue the role of cell cycle arrest in stress adaptation. We found that decoupling the stress response program from the cell cycle led to an adaptive program that was accelerated compared to the wild type strain. Furthermore, we uncovered that stress-induced cell cycle arrest restricted the utilization of metabolic resources, whereas unabated cell cycle progression diverted a surplus into the stress adaptation response. To probe why a wild type cell would ration its metabolic resources for an ostensibly suboptimal response, we identified an adaptive tradeoff that makes this rationing of resources advantageous under repeated stress. Given the universality of cell cycle regulation in stress responses, we suggest that this study might present a new paradigm in which the coordinated action of stress responses, cell cycle and metabolism help cells navigate the tradeoffs between rapid stress adaptation and long-term robustness.

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