The interaction of ATM and related protein kinases such as ATR and DNA-PK with p53 is disclosed, in particular the phosphorylation of Ser15 and Thr18 by these proteins. The activity of the proteins is shown to increase in the presence of DNA. Assays for modulators of phosphorylation by the interaction between the proteins and p53 or other proteins having similar phosphorylation sites are provided. Methods of purifying ATM or ATR employing DNA or NTA are also disclosed.