title: Effect of S. cerevisiae APN1 protein on mammalian DNA base excision repair.
abstract: Mammalian cells transfected with the S. cerevisiae APN1 protein acquire resistance to oxidizing agents, the damage of which are mainly repaired via DNA base excision repair (BER). We have recently hypothesized that this effect might be linked to the possible capacity of APN1 to accelerate mammalian BER by its 3' diesterase activity. We have investigated here the effect of pure APN1 protein on BER performed by mouse embryonic fibroblast extracts. No significant acceleration was observed in the repair of either a single AP site cleaved by the bifunctional glycosylase NTH of E. coli or the repair of a single 8-oxoguanine, initiated by the bifunctional glycosylase OGG1. Similarly, no significant effect was observed on the repair of a single U (initiated by the monofunctional glycosylase U DNA glycosylase) or the repair of a single natural abasic site. The inability of APN1 to increase the efficiency of BER initiated by bifunctional glycosylases indicates that removal of 3' blocking fragments is not the rate limiting step of this repair pathway.
authors.affiliation: DNA Repair Unit, Mutagenesis Laboratory, Istituto Nazionale Ricerca Cancro, 16132 Genova, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bogliolo
authors.forename: Enrico
authors.initials: E
authors.lastname: Cappelli
authors.forename: Andrea
authors.initials: A
authors.lastname: D'Osualdo
authors.forename: Ottavio
authors.initials: O
authors.lastname: Rossi
authors.forename: Ottavia
authors.initials: O
authors.lastname: Barbieri
authors.forename: Mark R
authors.initials: MR
authors.lastname: Kelley
authors.forename: Guido
authors.initials: G
authors.lastname: Frosina
mesh_terms: D000818:Animals; D002457:Cell Extracts / Q000737:chemistry; D004260:DNA Repair / Q000187:drug effects* / Q000502:physiology; D045643:DNA Repair Enzymes; D043382:DNA-Formamidopyrimidine Glycosylase; D004706:Endodeoxyribonucleases / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D005347:Fibroblasts / Q000737:chemistry; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology; D051379:Mice; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D002457:Cell Extracts; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D005982:Glutathione Transferase; D004706:Endodeoxyribonucleases; C083274:Apn1 protein, S cerevisiae; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; D045643:DNA Repair Enzymes