Gel Electrophoresis As a Method for Classifying Inhibitors of Poly(ADP-ribose) Polymerases 1 and 2

Poly(ADP-ribose) polymerases 1 and 2 (PARP1 and PARP2) play an important role in DNA damage repair in cells, and their inhibition is used for the treatment of certain oncological diseases. New PARP inhibitors are being actively developed and their mechanisms are being studied. This work shows that polyacrylamide gel electrophoresis of DNA complexes with PARP1 and PARP2 in the presence of inhibitors allows us to identify their effect on enzyme binding to DNA, as demonstrated by the inhibitors talazoparib, olaparib and veliparib. After addition of the substrate NAD+, this system can compare the efficiency of inhibition of the catalytic activity of PARP1 or PARP2 by the test compounds. It is crucial to consider both mechanisms for the search for new PARP1 and PARP2 inhibitors.