Effect of S. cerevisiae APN1 protein on mammalian DNA base excision repair.
Mammalian cells transfected with the S. cerevisiae APN1 protein acquire resistance to oxidizing agents, the damage of which is 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.
Bogliolo
Massimo
M
DNA Repair Unit, Mutagenesis Laboratory, Istituto Nazionale Ricerca Cancro, 16132 Genova, Italy.
Cappelli
Enrico
E
D'Osualdo
Andrea
A
Rossi
Ottavio
O
Barbieri
Ottavia
O
Kelley
Mark R
MR
Frosina
Guido
G
D000818:Animals; D002478:Cells, Cultured; D045647:DNA Glycosylases / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects* / Q000502:physiology; D045643:DNA Repair Enzymes; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D005347:Fibroblasts; D005982:Glutathione Transferase / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*
D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C024829:8-hydroxyguanine; D006147:Guanine; D005982:Glutathione Transferase; D004706:Endodeoxyribonucleases; C083274:Apn1 protein, S cerevisiae; D045647:DNA Glycosylases; D045643:DNA Repair Enzymes