Dissecting the Differences between the a and b Anomers of the Oxidative DNA Lesion FaPydG

Chemistry, 2008, 14, 2125-32 published on 14.01.2008
Chemistry, online article
The oxidative DNA lesion, FaPydG rapidly anomerizes to form a mixture of the a and b anomer. To investigate the mutagenic potential of both forms, we prepared stabilized bioisosteric analogues of both configurational isomers and incorporated them into oligonucleotides. These were subsequently used for thermodynamic melting-point studies and for primerextension experiments. While the b compound, in agreement with earlier data, prefers cytidine as the pairing partner, the a compound is not able form a stable base pair with any natural base. In primer-extension studies with the high-fidelity polymerase Bst Pol I, the polymerase was able to read through the lesion. The b compound showed no strong mutagenic potential. The a compound, in contrast, strongly destabilized DNA duplexes and also blocked all of the tested DNA polymerases, including two low-fidelity polymerases of the Y-family.

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