Meta-Biol

• Pathways

PARP inihibitors that block catalytic activity of PARP1 (or PARP2) bound to single-stranded DNA (ssDNA), including PARP1 and PARP2 autoPARylation (auto-polyADPribosylation), also inhibit microhomology-mediated end joining (MMEJ). Thus, the catalytic activity of PARP1 (or PARP2), related to autoPARylation or PARylation of other proteins at MMEJ site, is necessary for the progression of MMEJ (Mansour et al. 2010, Ceccaldi et al. 2015). By analogy with the DNA polymerase beta (POLB)-dependent long patch base excision repair (Satoh et al. 1994, Prasad et al. 2001), autoPARylated PARPs dissociate from the repair site, thereby coordinating the termination of strand displacement DNA synthesis and the cleavage of displaced strand flaps by FEN1.