A proposed mechanism for the mutagenicity of 5-formyluracil

Eric J. Privat; Lawrence C. Sowers

doi:10.1016/0027-5107(96)00005-X

A proposed mechanism for the mutagenicity of 5-formyluracil

Eric J. Privat, Lawrence C. Sowers

Research output: Contribution to journal › Article › peer-review

77 Scopus citations

Abstract

5-Formyluracil is a mutagenic base formed in DNA by oxidation of the thymine methyl group. Whereas the thymine methyl group is electron donating, the formyl group is electron withdrawing, predicting increased ionization of the N-3 imino proton under physiological conditions. The pK(a) values of a series of 5-substituted uracil and deoxyuridine derivatives have been measured. A linear relationship is observed between the electronic inductive property of the 5-substituent and the pK(a) value of the corresponding imino proton. The pK(a) value of 5-formyl-2'-deoxyuridine is close to that of the mutagenic nucleoside analogue 5-bromo-2'-deoxyuridine. In analogy with BrU, it is proposed that the mutagenicity of 5-formyluracil results from enhanced mispairing of the ionized form with guanine during DNA replication.

Original language	English (US)
Pages (from-to)	151-156
Number of pages	6
Journal	Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume	354
Issue number	2
DOIs	https://doi.org/10.1016/0027-5107(96)00005-X
State	Published - Jul 22 1996
Externally published	Yes

Keywords

5-Formyluracil
Mutagenic mechanism
Oxidized base

ASJC Scopus subject areas

Molecular Biology
Genetics
Health, Toxicology and Mutagenesis

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10.1016/0027-5107(96)00005-X

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title = "A proposed mechanism for the mutagenicity of 5-formyluracil",

abstract = "5-Formyluracil is a mutagenic base formed in DNA by oxidation of the thymine methyl group. Whereas the thymine methyl group is electron donating, the formyl group is electron withdrawing, predicting increased ionization of the N-3 imino proton under physiological conditions. The pK(a) values of a series of 5-substituted uracil and deoxyuridine derivatives have been measured. A linear relationship is observed between the electronic inductive property of the 5-substituent and the pK(a) value of the corresponding imino proton. The pK(a) value of 5-formyl-2'-deoxyuridine is close to that of the mutagenic nucleoside analogue 5-bromo-2'-deoxyuridine. In analogy with BrU, it is proposed that the mutagenicity of 5-formyluracil results from enhanced mispairing of the ionized form with guanine during DNA replication.",

keywords = "5-Formyluracil, Mutagenic mechanism, Oxidized base",

author = "Privat, {Eric J.} and Sowers, {Lawrence C.}",

note = "Funding Information: We thank Alicia Dwyer for assistancein the preparationof this manuscriptT.h is work was sup- ported in part by grants GM41336, GM50351, CA33572f rom the NationalI nstituteso f Health.",

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doi = "10.1016/0027-5107(96)00005-X",

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T1 - A proposed mechanism for the mutagenicity of 5-formyluracil

AU - Privat, Eric J.

AU - Sowers, Lawrence C.

N1 - Funding Information: We thank Alicia Dwyer for assistancein the preparationof this manuscriptT.h is work was sup- ported in part by grants GM41336, GM50351, CA33572f rom the NationalI nstituteso f Health.

PY - 1996/7/22

Y1 - 1996/7/22

N2 - 5-Formyluracil is a mutagenic base formed in DNA by oxidation of the thymine methyl group. Whereas the thymine methyl group is electron donating, the formyl group is electron withdrawing, predicting increased ionization of the N-3 imino proton under physiological conditions. The pK(a) values of a series of 5-substituted uracil and deoxyuridine derivatives have been measured. A linear relationship is observed between the electronic inductive property of the 5-substituent and the pK(a) value of the corresponding imino proton. The pK(a) value of 5-formyl-2'-deoxyuridine is close to that of the mutagenic nucleoside analogue 5-bromo-2'-deoxyuridine. In analogy with BrU, it is proposed that the mutagenicity of 5-formyluracil results from enhanced mispairing of the ionized form with guanine during DNA replication.

AB - 5-Formyluracil is a mutagenic base formed in DNA by oxidation of the thymine methyl group. Whereas the thymine methyl group is electron donating, the formyl group is electron withdrawing, predicting increased ionization of the N-3 imino proton under physiological conditions. The pK(a) values of a series of 5-substituted uracil and deoxyuridine derivatives have been measured. A linear relationship is observed between the electronic inductive property of the 5-substituent and the pK(a) value of the corresponding imino proton. The pK(a) value of 5-formyl-2'-deoxyuridine is close to that of the mutagenic nucleoside analogue 5-bromo-2'-deoxyuridine. In analogy with BrU, it is proposed that the mutagenicity of 5-formyluracil results from enhanced mispairing of the ionized form with guanine during DNA replication.

KW - 5-Formyluracil

KW - Mutagenic mechanism

KW - Oxidized base

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A proposed mechanism for the mutagenicity of 5-formyluracil

Abstract

Keywords

ASJC Scopus subject areas

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