Figure 1. Summary of PIKK Activation pathways. Preferential DNA substrates and recognition complexes are presented. (A) ATM responds to long 3′ single stranded regions via the MRN complex. (B) ATR is activated by short 3′ regions near duplex junctions via RPA:ATRIP and TopBP1. Protein complexes that tether the PIKKs to DNA are colored green while proteins involved in activating the PIKKs are indicated by the squares. (C) DNA-PKcs recognizes double stranded DNA termini via Ku.