Model for resection of neat DSBs in LSS and HSS. In LSS, resection can be initiated by Exo1, in an ATM-independent manner (a), or by CtIP-MRN in an ATM-dependent manner (b). In HSS, Exo1 is not active and resection is initiated by CtIP-MRN in an ATM-dependent manner (b). Initiation by either pathway allows clipping of DSBs to provide sufficient RPA-ssDNA to locally activate ATR (c). ATR then phosphorylates CtIP on T818, which is essential for stable CtIP chromatin-binding, and downstream extension of resection tracts by a DNA2-dependent mechanism.