Excision by the human methylpurine DNA N‐glycosylase of cyanuric acid, a stable and mutagenic oxidation product of 8‐oxo‐7,8‐dihydroguanine

Purpose: 1‐(2‐Deoxy‐β‐D‐erythro‐pentofuranosyl)‐cyanuric acid (cyanuric acid nucleoside or dCa) has been shown to be formed upon exposure of 8‐oxo‐7,8‐dihydroguanine‐ (8‐oxoG) containing oligodeoxyribonucleotides (ODN) to oxidizing agents. When present in DNA, cyanuric acid (Ca) is readily bypassed by Escherichia coli DNA polymerases, which preferentially incorporate 2′‐deoxyadenosine‐5′‐monophosphate (dAMP) opposite to the lesion. Therefore, Ca could be a mutagenic DNA lesion yielding G.C to T.A transversions like 8‐oxoG. These results call attention to the potential importance of secondary oxidation products of 8‐oxoG. The present study investigates the capability of several DNA N‐glycosylases to remove the Ca lesion in DNA.Materials and methods: A site‐specifically modified 22‐mer ODN containing a single Ca residue was hybridized with complementary sequences yielding four DNA duplexes harbouring Ca opposite each of the regular DNA bases. The four Ca.N duplexes were used as substrates for nine DNA N‐gly...