The alkyltransferase-like ybaZ gene product enhances nucleotide excision repair of O(6)-alkylguanine adducts in E. coli.
O(6)-methylguanine adducts are potent pre-mutagenic lesions owing to their high capacity to direct mis-insertion of thymine when bypassed by replicative DNA polymerases. The strong mutagenic potential of these adducts is prevented by alkyltransferases such as Ada and Ogt in Escherichia coli that transfer the methyl group to one of their cysteine residues. Alkyl residues larger than methyl are generally weak substrates for reversion by alkyltransferases. In this paper we have investigated the genotoxic potential of the O(6)-alkylguanine adducts formed by ethylene and propylene oxide using single-adducted plasmid probes. Our work shows that the ybaZ gene product, a member of the alkyltransferase-like protein family, strongly enhances the repair by nucleotide excision repair of the larger O(6)-alkylguanine adducts that are otherwise poor substrates for alkyltransferases. The YbaZ protein is shown to interact with UvrA. This factor may thus enhance the efficiency of nucleotide excision repair in a way similar to the Transcription-Repair Coupling factor Mfd, by recruiting the UvrA(2).UvrB complex to the adduct site via its interaction with UvrA.
Mazon
Gerard
G
CNRS, UPR 3081, Genome Instability and Carcinogenesis, Conventionné par l'Université d'Aix-Marseille 2, 31, Chemin Joseph Aiguier, 13402 Marseille cedex 20, France.
Philippin
Gaëlle
G
Cadet
Jean
J
Gasparutto
Didier
D
Fuchs
Robert P
RP
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D019883:Alkyl and Aryl Transferases / Q000235:genetics* / Q000378:metabolism; D018736:DNA Adducts / Q000235:genetics*; D004260:DNA Repair; D004269:DNA, Bacterial / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D005798:Genes, Bacterial / Q000502:physiology*; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D016296:Mutagenesis; D009154:Mutation; D012293:Rifampin / Q000494:pharmacology
D018736:DNA Adducts; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C064976:O(6)-benzylguanine; D006147:Guanine; D019883:Alkyl and Aryl Transferases; C068631:UvrA protein, E coli; D000251:Adenosine Triphosphatases; D012293:Rifampin