Mutations that disrupt crucial cellular processes, such as DNA replication, frequently result in significant impairments in growth. When these defects are not lethal, they exert substantial selective pressure on cells, often leading to pathological conditions such as cancer and premature aging. Recent investigations have elucidated the rapid evolutionary adaptations of cells to mutations, even when they disrupt essential and conserved processes. Constitutive exposure of cells to replication stress instigates the accumulation of DNA damage and, ultimately, genetic instability. Presently, the impact of environmental cues on the evolutionary adaptation to intracellular selective pressure remains unknown. Among these cues, nutrient availability is a prominent variable influencing several processes, including regulating the cell cycle and ensuring that these processes occur only under favorable conditions. In this project, we investigated the influence of nutrient availability and nutrient sensing on the evolutionary adaptation to DNA replication stress. Our findings demonstrate that although various nutrient conditions affect cell growth and the cell cycle, the evolutionary strategies enabling cells to adapt to DNA replication stress are conserved. These results underscore the robustness of this evolutionary process in the face of environmental fluctuations. The implications of our research are pertinent to the identification of potential therapeutic targets for the treatment of tumors or genetic diseases associated with premature aging.
