TI - PARP inhibitors promote ATM activation through induction of DSBs . AB - To gain insight about the increased basal ATM-kinase activity after the inhibition of PARP-1 with ANI ( figure 2C ) , we performed an indirect inmunofluorescence against H2AX in its PHOSphorylated form , after the incubation with the PARP inhibitor in order to detect any DNA damage response . ATM wild type and deficient cells ( G361 and HT144 respectively ) were incubated with ANI at different times . Remarkably the sole fact of the incubation with ANI was able to elicits H2AX PHOSphorylation in wild type but not in ATM deficient cells . This effect was transient and reached a peak in 2 hours , declining afterwards ( figure 3 ) . gamma-Irradiation was used as positive internal control ( figure 3 , upper panels ) . Previous results from our group have shown that PARP-1 null cells have a deficient p53 Ser15 phosphorylaTION in response to ionising radiation [15] , confirming with a different ATM SUBstrate that ATM activation is compromised in the absence of PARP-1 . Recent results have shown that inhibition of PARP leads to stalled replication fork and the formation of DNA double strand breaks that are resolved by homologous recombination [17] . In order to test this possibility in our system we performed neutral comet assay to detect double strand breaks ( DSB ) . DSB were produced by treatment with the PARP inhibitor in both ATM proficient ( G361 ) and deficient ( HT144 ) cells but only ATM wild type cells were able to completely resolve double strand breaks ( figure 4A ) . PARP inhibition activates ATM through the induction of DSBs which are repaired by HR ; since ATM deficient cells were less efficient in resolving DNA strand breaks that result from PARP inhibition we next examined their sensitivity to ANI in the presence and absence of IR . Results in figure 4B clearly show that ATM deficient cells are much more sensitive to PARP inhibition with or without further DNA damage .