title: The mutagenic potential of 8-oxoG/single strand break-containing clusters depends on their relative positions.
abstract: The biological consequences of clusters containing a single strand break and base lesion(s) remain largely unknown. In the present study we determined the mutagenicities of two- and three-lesion clustered damage sites containing a 1-nucleotide gap (GAP) and 8-oxo-7,8-dihydroguanine(s) (8-oxoG(s)) in Escherichia coli. The mutation frequencies (MFs) of bi-stranded two-lesion clusters (GAP/8-oxoG), especially in mutY-deficient strains, were high and were similar to those for bi-stranded clusters with 8-oxoG and base lesions/AP sites, suggesting that the GAP is processed with an efficiency similar to the efficiency of processing a base lesion or an AP site within a cluster. The MFs of tandem two-lesion clusters comprised of a GAP and an 8-oxoG on the same strand were comparable to or less than the MF of a single 8-oxoG. The mutagenic potential of three-lesion clusters, which were comprised of a tandem lesion (a GAP and an 8-oxoG) and an opposing single 8-oxoG, was higher than that of a single 8-oxoG, but was no more than that of a bi-stranded 8-oxoGs. We suggest that incorporation of a nucleotide opposite 8-oxoG is less mutagenic when a GAP is present in a cluster than when a GAP is absent. Our observations indicate that the repair of a GAP is retarded by an opposing 8-oxoG, but not by a tandem 8-oxoG, and that the extent of GAP repair determines the biological consequences.
authors.affiliation: Advanced Research Science Center, Japan Atomic Energy Agency, 2-4 Shirakata-Shirane, Tokai-mura, Ibaraki 319-1195, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Noguchi
authors.forename: Ayumi
authors.initials: A
authors.lastname: Urushibara
authors.forename: Akinari
authors.initials: A
authors.lastname: Yokoya
authors.forename: Peter
authors.initials: P
authors.lastname: O'Neill
authors.forename: Naoya
authors.initials: N
authors.lastname: Shikazono
mesh_terms: D053904:DNA Breaks, Single-Stranded; D004260:DNA Repair; D003839:Deoxyadenosines / Q000235:genetics*; D004926:Escherichia coli; D016296:Mutagenesis; D059645:Mutation Rate; D010957:Plasmids / Q000235:genetics
chemical_list: D003839:Deoxyadenosines; C078251:2'-deoxy-7,8-dihydro-8-oxoadenosine