The April 2017 Editor's Choice article is "Error-Prone Replication Bypass of the Imidazole Ring-Opened Formamidopyrimidine Deoxyguanosine Adduct” by Yan Sha, Irina G. Minko, Chanchal K. Malik, Carmelo J. Rizzo, and R. Stephen Lloyd.
Damage to DNA caused by reactive oxygen species promotes mutagenesis, carcinogenesis and aging. In the April 2017 issue of Environmental and Molecular Mutagenesis, Yan Sha and coworkers at the Oregon Health & Science University and Vanderbilt University examined the impact of local sequence context and anomeric conformation (α or β) on Fapy-dG adduct-induced mutagenesis. The investigators synthesized oligonucleotides containing the Fapy-dG adduct bracketed by different nucleotides and designed a strategy for inserting the nucleotides into a vector that could be replicated in E. coli or primate cells. Replication of the Fapy-dG adduct yielded primarily G to A base substitution mutations. By comparing constructs in which the adduct was present in different sequence contexts, Sha et al. showed the mutations occurred by direct misincorporation, rather than through a primer/template misalignment mechanism. The mutagenic contributions of the α and β anomeric conformations of Fapy-dG were interrogated by treating some of the Fapy-dG-containing duplex DNA with E. coli Endonuclease IV, an enzyme that cleaves DNA containing the α form. Eliminating the α form reduced the observed mutagenesis, thereby demonstrating that a subset of Fapy-dG-induced mutations are due to error-prone bypass of the α anomeric form.
Reactive oxygen species can be generated as a consequence of chronic inflammation and exposure to ionizing radiation or chemotherapy. Given the importance of understanding the mutagenic potential of DNA base damage generated by the reactive oxygen species and the exacting nature of the experiments reported, this article was selected as the “Editor’s Choice” for the April issue of Environmental and Molecular Mutagenesis. Environ. Mol. Mutagen. 58: 184-189, 2017. © 2017 Wiley Periodicals, Inc.