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In hopes of gathering this kind of detail about the cellular processing and biological relevancy of other kinds of oxidative DNA modifications, chemists are racing to make oligonucleotides containing these oxidation lesions. Marc M. Greenberg, an organic chemistry professor at Johns Hopkins University, recently developed a method for constructing oligonucleotides containing defined Fapy-G lesions [J. Am. Chem. Soc., 124, 3263 (2002)]. It's been shown that Fapy-G lesions form more readily than 8-oxoguanine under some conditions, both in vivo and in vitro. But until very recently, Fapy-G lesions have been underappreciated--in part because oligonucleotides containing Fapy-G were synthetically inaccessible, Greenberg says. His lab has shown that Fapy-G can cause the same deleterious guanine:cytosine to thymine:adenine mutations in vitro as 8-oxoguanine does [J. Am. Chem. Soc., 124, 7278 (2002)]. Plus, he tells C&EN, his lab has unpublished evidence showing that Fapy-G causes mutations in bacteria at a significant rate. Could FapyG be more dangerous than 8-oxoguanine? "It's too early to tell," Greenberg says. "But it shouldn't be overlooked." |
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