Incorporation by chemical synthesis and characterization of deoxyribosylformylamine into DNA

Guy, A.; Duplaa, A.M.; Ulrich, J.; Téoule, R.

doi:10.1093/nar/19.21.5815

Cited by 27 publications

(15 citation statements)

References 28 publications

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“…The DMDO oxidations of dGuo and dGMP conform to expectation; both starting compounds yield two diastereomers in a ∼ 2:1 mixture. In addition, slow rotation around the N8-C9 formamido bond resulted in resolution of two rotational isomers for each diastereomer, analogous to behavior reported for the 2-Ih base22 and the N -(2′-deoxyribosyl)formamide lesion29,30. The major rotational isomers of the 2-Ih diastereomers at the deoxynucleoside level were favored by an order of magnitude over the minor rotamers.…”

Section: Discussionsupporting

confidence: 64%

Iminohydantoin Lesion Induced in DNA by Peracids and Other Epoxidizing Oxidants

Ye¹,

Sangaiah²,

Degen³

et al. 2009

J. Am. Chem. Soc.

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The oxidation of guanine to 5-carboxamido-5-formamido-2-iminohydantoin (2-Ih) is shown to be a major transformation in the oxidation of the single-stranded DNA 5-mer d(TTGTT) by m-CPBA and DMDO as a model for peracid oxidants and in the oxidation of the 5-base pair duplex d[(TTGTT)·(AACAA)] with DMDO. 2-Ih has not been reported as an oxidative lesion at the level of single/double-stranded DNA or at the nucleoside/nucleotide level. The lesion is stable to DNA digestion and chromatographic purification suggesting that 2-Ih may be a stable biomarker in vivo. The oxidation products have been structurally characterized and the reaction mechanism probed by oxidation of the monomeric species dGuo, dGMP and dGTP. DMDO selectively oxidizes the guanine moiety of dGuo, dGMP and dGTP to 2-Ih, and both peracetic and m-chloroperbenzoic acids exhibit the same selectivity. The presence of the glycosidic bond results in the stereoselective induction of an asymmetric center at the spiro carbon to give a mixture of diastereomers, with each diastereomer in equilibrium with a minor conformer through rotation about the formamido C-N bond. Labeling studies with 18O2-m-CPBA and H218O to determine the source of the added oxygen atoms have established initial epoxidation of the guanine 4-5 bond with pyrimidine ring contraction by an acyl 1,2-migration of guanine carbonyl C6 to form a transient dehydrodeoxyspiroiminodihydantoin followed by hydrolytic ring opening of the imidazolone ring. Consistent with the proposed mechanism, no 8-oxoguanine was detected as a product of the oxidations of the oligonucleotides or monomeric species mediated by DMDO or the peracids. The 2-Ih base thus appears to be a pathway-specific lesion generated by peracids and possibly other epoxidizing agents and holds promise as a potential biomarker.

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Section: Discussionsupporting

confidence: 64%

Iminohydantoin Lesion Induced in DNA by Peracids and Other Epoxidizing Oxidants

Ye¹,

Sangaiah²,

Degen³

et al. 2009

J. Am. Chem. Soc.

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“…The decamer containing the N-(2-deoxy-b-D-erythropentofuranosyl) formamide residue was synthesized as previously reported (Guy et al 1991).…”

Section: Synthesismentioning

confidence: 99%

“…It was shown (Guy et al 1991) that base fragmentation products can be bypassed by DNA polymerase or that the presence of formamide can either promote nucleotide incorporation or induce a deletion.…”

Section: Biological Implicationmentioning

confidence: 99%

“…It involves the one-electron oxidation of thymine or cytosine as the result of ionization through initial formation of the related pyrimidine radical cation and subsequent hydration giving rise to the corresponding 6-hydroxy-5,6-dihydropyrimidyl radical (Decarroz et al 1986;Wagner et al 1999). DNA polymerase bypasses fragmentation base products like formamide with an estimated frequency of 33 and 11% for the Klenow fragment and Taq DNA polymerase, respectively, thus giving rise to a frameshift mutation (Guy et al 1991). However, the formamide lesion also appears to be able to direct nucleotide incorporation, preferentially of guanine, but also of adenine.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Solution structure of a DNA duplex containing a formamide-adenine base pair

Maufrais

Boulard²

2002

Can. J. Physiol. Pharmacol.

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The N-(2-deoxy-beta3-D-erythro-pentofuranosyl) formamide residue results from a ring fragmentation product of thymine or cytosine. The presence of a formamide-adenine base pair in the sequence 5'd(AGGAACCACG).d(CGTGGFTCCT) has been studied by 1H and 31P nuclear magnetic resonance (NMR) and molecular dynamics. There are two possible isomers for the formamide side chain, either cis or trans. For each isomer, we observed an equilibrium in solution between two forms. First, a species where the formamide is intrahelical and paired with the facing adenine. For the cis isomer, the formamide is in a syn conformation and two hydrogen bonds with adenine are formed. The trans isomer is in an anti conformation and a single hydrogen bond is observed. In the second form, whatever the isomer, the formamide is rejected outside the helix, whereas the adenine remains inside.

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“…8-Oxo-7,8-dihydro-2 0 -deoxyguanosine (8-oxodGuo), which is miscoding and mutagenic [9], is considered one of the most important DNA markers of the oxidation processes within cells [7]. Furthermore formylamine (N-(deoxy-b-D D-erythropentofuranosyl)-formylamine; dF), a major oxidative DNA lesion formed upon ionizing irradiation [10], was added. The latter lesion is considered an abasic site by certain authors [11].…”

mentioning

confidence: 99%