**9. Nutrient sensing and the regulation of adaptation and the checkpoint response**

One unifying theme in DNA damage tolerance to multiple types of DNA lesions is that nutrient sensing plays an important role in promoting downregulation of the checkpoint response. Deregulation of *IRA1* and *IRA2*, which control glucosegrowth signaling, prevent adaptation to uncapped telomeres in *cdc13* strains [155]. Inhibition of TOR1 by rapamycin prevents adaptation and aneuploidy in rad52 diploid strains exposed to DNA damaging agents [156].

Nutrient sensing is also important in controlling the checkpoint response through type 2A protein phosphatases. In the presence of plentiful carbon and nitrogen, target of rapamycin (TORC1) activates Mec1-signaling pathway by inhibiting PP2A and PP2A-like phosphatases. PP2A activators include ceramide and S-adenosyl methionine (SAM) [139]. The effect of this signaling on the PP2C and PP4 phosphatases is unclear. Nonetheless, these studies illustrate that the DNA damage response requires an active growth signaling response [139]. Recent data also suggests that TORC1 inhibition results in lower levels of checkpoint proteins [157]. Thus, it may appear that TORC1 may be required for both checkpoint activation and for adaptation.
