Base excision repair is impaired in mammalian cells lacking poly(ADP-ribose) polymerase-1

In mammalian cells, damaged bases in DNA are corrected by the base excision repair pathway which is divided into two distinct pathways depending on th e length of the resynthesized patch, replacement of one nucleotide for shor t-patch repair, and resynthesis of several nucleotides for long-patch repai r. The involvement of poly(ADP-ribose) polymerase-1 (PARP-1) in both pathwa ys has been investigated by using PARP-1-deficient cell extracts to repair single abasic sites derived from uracil or 8-oxoguanine located in a double -stranded circular plasmid. For both lesions, PARP-1-deficient cell extract s were about half as efficient as wild-type cells at the polymerization ste p of the short-patch repair synthesis, but were highly inefficient at the l ong-patch repair. We provided evidence that PARP-1 constitutively interacts with DNA polymerase beta. Using cell-free extracts from mouse embryonic ce lls deficient in DNA polymerase beta, we demonstrated that DNA polymerase b eta is involved in the repair of uracil-derived AP sites via both the short and the long-patch repair pathways. When both PARP-1 and DNA polymerase be ta were absent, the two repair pathways were dramatically affected, indicat ing that base excision repair was highly inefficient. These results show th at PARP-1 is an active player in DNA base excision repair.