**10. Concluding remarks**

Adaptation to DNA damage is critical for cell survival. The simple, straightforward model is that DNA damage activates checkpoint signaling kinases and that phosphatases, which are constitutively expressed, serve to dephosphorylate and deactivate phosphorylated proteins. Once the DNA damage is repaired, the checkpoint signaling ceases and activated proteins are dephosphorylated. However, yeast can adapt to DNA damage caused by diverse damaging agents and individual phosphatases are controlled by different kinases. In addition, cells exposed to different DNA damaging agents exhibit distinct Rad53 phosphorylation patterns and rely more on particular phosphatases for checkpoint adaptation. The checkpoint pathway also autoregulates itself and dampens its signaling in coordination with Cdk1. Finally, adaptation to particular DNA damage requires TORC1 function, which senses nutrient abundance. Thus, simple models are likely complicated by the complexity of the checkpoint responses elicited by distinct DNA damaging agents.
