title: Interaction between the mismatch repair and nucleotide excision repair pathways in the prevention of 5-azacytidine-induced CG-to-GC mutations in Escherichia coli.
abstract: 5-Azacytidine induces CG-to-GC transversion mutations in Escherichia coli. The results presented in this paper provide evidence that repair of the drug-induced lesions that produce these mutations involves components of both the mismatch repair and nucleotide excision repair systems. Strains deficient in mutL, mutS, uvrA, uvrB or uvrC all showed an increase in mutation in response to 5-azacytidine. Using a bacterial two-hybrid assay, we showed that UvrB interacts with MutL and MutS in a drug-dependent manner, while UvrC interacts with MutL independent of drug. We suggest that 5-azacytidine-induced mismatches recruit MutS and MutL, but are poorly processed by mismatch repair. Instead, the stalled MutS-MutL complex recruits the Uvr proteins to complete repair.
authors.affiliation: Biology Department, Concordia University, Montreal, Que, Canada.
authors.forename: Photini
authors.initials: P
authors.lastname: Pitsikas
authors.forename: Yaroslava Y
authors.initials: YY
authors.lastname: Polosina
authors.forename: Claire G
authors.initials: CG
authors.lastname: Cupples
mesh_terms: D000251:Adenosine Triphosphatases / Q000172:deficiency / Q000187:drug effects; D001374:Azacitidine / Q000008:administration & dosage*; D020137:Base Pair Mismatch / Q000187:drug effects*; D004265:DNA Helicases / Q000172:deficiency / Q000187:drug effects; D053843:DNA Mismatch Repair / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology*; D045643:DNA Repair Enzymes / Q000172:deficiency / Q000187:drug effects; D004269:DNA, Bacterial / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000187:drug effects; D015257:DNA-Cytosine Methylases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004706:Endodeoxyribonucleases / Q000172:deficiency / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000187:drug effects; D016368:Frameshift Mutation / Q000187:drug effects; D000070956:MutL Proteins; D051719:MutS DNA Mismatch-Binding Protein / Q000172:deficiency / Q000187:drug effects; D020798:Two-Hybrid System Techniques
chemical_list: D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; C074770:MutL protein, E coli; C058093:UvrB protein, E coli; D015257:DNA-Cytosine Methylases; D004706:Endodeoxyribonucleases; C059682:methyl-directed mismatch repair protein, E coli; C066567:UvrC protein, E coli; C068631:UvrA protein, E coli; D000251:Adenosine Triphosphatases; D000070956:MutL Proteins; D051719:MutS DNA Mismatch-Binding Protein; D004265:DNA Helicases; D045643:DNA Repair Enzymes; D001374:Azacitidine