A proposed mechanism for the mutagenicity of 5-formyluracil

Eric J. Privat, Lawrence Sowers

Research output: Contribution to journalArticle

70 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)151-156
Number of pages6
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume354
Issue number2
DOIs
StatePublished - Jul 22 1996
Externally publishedYes

Fingerprint

Thymine
Protons
Electrons
Deoxyuridine
Uracil
Guanine
Bromodeoxyuridine
DNA Replication
Nucleosides
DNA
5-formyluracil
5-formyl-2'-deoxyuridine

Keywords

  • 5-Formyluracil
  • Mutagenic mechanism
  • Oxidized base

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Molecular Biology

Cite this

A proposed mechanism for the mutagenicity of 5-formyluracil. / Privat, Eric J.; Sowers, Lawrence.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 354, No. 2, 22.07.1996, p. 151-156.

Research output: Contribution to journalArticle

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