title: Near ultraviolet radiation (UVA and UVB) causes a formamidopyrimidine glycosylase-dependent increase in G to T transversions.
abstract: In contrast to far-UV (< 290 nm) DNA damage, a large fraction of the DNA damage caused by near-UV is oxygen-dependent, suggesting the involvement of reactive oxygen species (ROS). The oxidized base 8-oxo-7,8-dihydroguanine (GO) is characteristic of ROS-induced DNA damage and is removed by Fapy (formamidopyrimidine) glycosylase. We have recently shown that Escherichia coli strains deficient in Fapy glycosylase (fpg) are hypersensitive to the lethal effects of UVA but not far-UV (UVC), suggesting lesions recognized by this enzyme may be important premutagenic or lethal lesions generated by near-UV radiation. In this study, we have found that while the far-UV-induced mutation rates of Fapy-deficient and wild-type strains were similar, near-UV (UVA and UVB) was hypermutagenic to a Fapy-deficient strain, causing a dose-dependent increase in induced mutation relative to wild type (up to five-fold at 200 kJ/m2). Using a plasmid back mutation assay, the predominant near-UV-induced mutations in both wild-type and Fapy-deficient strains were found to be C-->T transitions and G -->T transversions. The former is probably due to replicative bypass of pyrimidine dimers or (6-4) photoproducts that are known to be generated by near-UV, whereas the latter may be due to mispairing of GO lesions with adenine during replication. Consistent with this, the frequency of near-UV-induced G-->T transversions was 16-fold higher in a Fapy-deficient strain than a wild-type strain.
authors.affiliation: Department of Biology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: C M
authors.initials: CM
authors.lastname: Palmer
authors.forename: D M
authors.initials: DM
authors.lastname: Serafini
authors.forename: H E
authors.initials: HE
authors.lastname: Schellhorn
mesh_terms: D043382:DNA-Formamidopyrimidine Glycosylase; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins; D006147:Guanine / Q000378:metabolism; D009699:N-Glycosyl Hydrolases / Q000235:genetics / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D029968:Escherichia coli Proteins; D006147:Guanine; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; C468610:DNA-formamidopyrimidine glycosylase, E coli; D013936:Thymidine