Drosophila S3 ribosomal protein accelerates repair of 8-oxoguanine performed by human and mouse cell extracts.
The S3 ribosomal protein of Drosophila melanogaster possesses various DNA repair activities, including the capacity to incise at apurinic/apyrimidinic (AP) sites and 8-oxo-7,8-dihydroguanine (8-oxoG) residues. We have recently hypothesized that this multifunctional protein may improve the efficiency of DNA base excision repair (BER) in mammalian cells. We have investigated the effect of pure GST-tagged Drosophila S3 on BER of different endogenous lesions performed by human and mouse cell extracts. Drosophila S3 significantly accelerated the BER of 8-oxoG (initiated by the bifunctional glycosylase OGG1). The stimulating effect was linked to the capacity of S3 to remove the 8-oxoG lesion and cleave the resulting AP site, rather than acceleration of downstream steps of the BER pathway (e.g., removal of 3' blocking fragments). No stimulating effect was observed on the BER of uracil, natural AP sites, and beta-lyase-cleaved AP sites. Heterologous expression of Drosophila S3 may be used to enhance 8-oxoG repair in human cells.
Cappelli
Enrico
E
DNA Repair Unit, Mutagenesis Laboratory - Istituto Nazionale Ricerca Cancro, Genova, Italy.
D'Osualdo
Andrea
A
Bogliolo
Massimo
M
Kelley
Mark R
MR
Frosina
Guido
G
D000818:Animals; D002457:Cell Extracts / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D043382:DNA-Formamidopyrimidine Glycosylase; D004331:Drosophila melanogaster / Q000502:physiology*; D005347:Fibroblasts / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D006151:Guanosine / Q000031:analogs & derivatives* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D009699:N-Glycosyl Hydrolases / Q000633:toxicity; D012269:Ribosomal Proteins / Q000302:isolation & purification / Q000494:pharmacology*
D002457:Cell Extracts; D012269:Ribosomal Proteins; C044152:ribosomal protein S3; D006151:Guanosine; C046215:8-hydroxyguanosine; D004247:DNA; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase