Our results demonstrate that pharmacological kinase inhibition of ATM reduced cyst growth in vitro and renal cell proliferation in vivo but that the long-term progression of cyst growth in a genetic ortholog of ADPKD was not altered by the reduction or loss of Atm. Furthermore, we noted that pharmacological ATR inhibition of ATR was associated with the development of dysplastic changes in cystic kidney epithelial cells in vitro. Here, ATR is linked to cyst.