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 the length of the resynthesized patch, replacement of one nucleotide for short-patch repair, and resynthesis of several nucleotides for long-patch repair. The involvement of poly(ADP-ribose) polymerase-1 (PARP-1) in both pathways 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 extracts were about half as efficient as wild-type cells at the polymerization step of the short-patch repair synthesis, but were highly inefficient at the long-patch repair. We provided evidence that PARP-1 constitutively interacts with DNA polymerase beta. Using cell-free extracts from mouse embryonic cells deficient in DNA polymerase beta, we demonstrated that DNA polymerase beta 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 beta were absent, the two repair pathways were dramatically affected, indicating that base excision repair was highly inefficient. These results show that PARP-1 is an active player in DNA base excision repair.
Dantzer
F
F
UPR 9003 du Centre National de la Recherche Scientifique "Cancérogenèse et Mutagenèse Moléculaire et Structurale", Illkirch-Graffenstaden, France.
de La Rubia
G
G
Ménissier-De Murcia
J
J
Hostomsky
Z
Z
de Murcia
G
G
Schreiber
V
V
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D019951:DNA Polymerase beta / Q000378:metabolism; D017931:DNA Primers; D004260:DNA Repair; D051379:Mice; D009243:NAD / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; D009243:NAD; D011065:Poly(ADP-ribose) Polymerases; D019951:DNA Polymerase beta