Perturbing the process using PARP inhibitors minimises the levels of PARylation, hindering recruitment of repair factors leading to unrepaired breaks. PARP inhibitors can have the additional effect of trapping PARP on DNA so that PARP is effectively “locked on” and NAD levels remain intact. 

Depletion or inhibition of PARG leads to sustained high levels of PARylation on PARP with NAD levels depleted. PARP can no longer bind DNA so is “locked off”.  PARG inhibitors increase sensitivity to DNA damaging agents and are currently being validated as a monotherapy in the clinic.