3. Mechanism of action of PARP (poly-ADP-ribose-polymerase). Single strand DNA damage induced by chemotherapeutic agents or radiotherapy is repaired by this enzyme leading to cell survival. In this process PARP accumulates ADP tails. However, big amounts of DNA damage cannot be repaired by PARP, so that, ADP tails are released and induce cell death (A). Mechanism of synthetic lethality. BER Base Excision Repair (RES) system repairs single chain DNA damage and Homologous recombination system (HRS) repair double strand DNA damage. These two systems are consecutive, so that, DNA damage and the ineffective of BER lead to the activation of HRS. HRS is made up by repair proteins like BRCA, ATM or ATR. Germinal of somatical mutations in these genes provoke an ineffective HRS dependent DNA repair. This fact could profit to trigger a syntetic lethality, inhibiting PARP with molecules such as olaparib. Therefore, the deffective HRS due to genetic mutations added to BER system inhibition by PARP blockers lead to apoptosis of cancer cells (B).