Does tautomerization of FapyG influence its mutagenicity?

Abstract

Oxidative degradation of guanine to 2,6-diamino-4-oxo-5-formamidopyrimidine (FapyG) is believed to be mutagenic. It has been proposed recently that the enol tautomer of FapyG is mainly responsible for this effect leading to a guanine-to-thymine mutation (T. H. Gehrke, U. Lischke, K. L. Gasteiger, S. Schneider, S. Arnold, H. C. Muller, D. S. Stephenson, H. Zipse, T. Carell, Nat. Chem. Biol. 2013, 9, 455-461). Here, density functional methods suggest that the enol tautomer of FapyG might not be responsible for the proposed guanine-to-thymine mutation. Instead, it might result in a guanine-to-adenine mutation. New mutation for FapyG: It is revealed that the enol tautomer of FapyG might lead to a guanine-to-adenine mutation, whereas its keto tautomer might induce a guanine-to-thymine mutation. The conformational flexibility of the N-glycosidic bond of FapyG might also play an important role in these mutations. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.