Function of BRCA1 in the DNA Damage Response Is Mediated by ADP-Ribosylation

“…Although the secondary structure and tertiary folding are similar among the PIN domains, the primary sequence is not conserved, which might provide the biochemical basis for the diversified functions of the PIN domains. Similar phenomena have been observed in the BRCT, FHA and OB-fold domains, three other poly (ADP-ribose) binding modules ( 13 , 14 , 17 , 30 ). Both the BRCT and FHA domains have been found as the phospho-amino acid binding modules ( 69 – 73 ).…”

“…Our results provide a benchmark for interpretation of the cellular effects of ten widely used PARP and tankyrase inhibitors. Previously, these effectors have regularly been used at micromolar concentrations, but effective cellular concentrations of PARP inhibitors are similar to our in vitro IC 50 values. ,− Thus, the results presented here provide relevant effector concentrations for experimental design to achieve either selective inhibition of PARP1 and -2 using veliparib, or broad inhibition of PARP enzymes using PJ34 or rucaparib. Moreover, they illustrate the importance of determining the relevant concentration regimes for PARP inhibitors used as chemical tools.…”

“…Thus, we investigated the chemotherapy effect of PARP inhibitor on the RNF8, Ku70, and FEN1 deficient primary cancer cells. As expected, both RNF8 and Ku70 deficient cancer cells were hypersensitive to PJ34 and olaparib, the two widely used PARP inhibitors [27, 59]. However, the chemotherapy efficiency on FEN1 deficient cells was weaker than those on RNF8 and Ku70 deficient cells (Figure 4D).…”