Repair of the mutagenic DNA oxidation product, 5-formyluracil

Pingfang Liu, Artur Burdzy, Lawrence Sowers

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The oxidation of the thymine methyl group can generate 5-formyluracil (FoU). Template FoU residues are known to miscode, generating base substitution mutations. The repair of the FoU lesion is therefore important in minimizing mutations induced by DNA oxidation. We have studied the repair of FoU in synthetic oligonucleotides when paired with A and G. In E. coli cell extract, the repair of FoU is four orders of magnitude lower than the repair of U and is similar for both FoU:A and FoU:G base pairs. In HeLa nuclear extract, the repair of FoU:A is similarly four orders of magnitude lower than the repair of uracil, although the FoU:G lesion is repaired 10 times more efficiently than FoU:A. The FoU:G lesion is shown to be repaired by E. coli mismatch uracil DNA glycosylase (Mug), thermophile mismatch thymine DNA glycosylase (Tdg), mouse mismatch thymine DNA glycosylase (mTDG) and human methyl-CpG-binding thymine DNA glycosylase (MBD4), whereas the FoU:A lesion is repaired only by Mug and mTDG. The repair of FoU relative to the other pyrimidines examined here in human cell extract differs from the substrate preferences of the known glycosylases, suggesting that additional, and as yet unidentified glycosylases exist in human cells to repair the FoU lesion. Indeed, as observed in HeLa nuclear extract, the repair of mispaired FoU derived from misincorporation of dGMP across from template FoU could promote rather than minimize mutagenesis. The pathways by which this important lesion is repaired in human cells are as yet unexplained, and are likely to be complex.

Original languageEnglish (US)
Pages (from-to)199-210
Number of pages12
JournalDNA Repair
Volume2
Issue number2
DOIs
StatePublished - Feb 3 2003
Externally publishedYes

Fingerprint

DNA Repair
Repair
Oxidation
DNA
Thymine DNA Glycosylase
Uracil-DNA Glycosidase
5-formyluracil
Cells
Cell Extracts
Escherichia coli
Pyrimidines
Mutagenesis
Mutation
Thymine
Uracil
Oligonucleotides
Base Pairing
Substitution reactions

Keywords

  • 5-Formyluracil
  • DNA repair
  • Mutagenesis
  • Oxidative DNA damage

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Repair of the mutagenic DNA oxidation product, 5-formyluracil. / Liu, Pingfang; Burdzy, Artur; Sowers, Lawrence.

In: DNA Repair, Vol. 2, No. 2, 03.02.2003, p. 199-210.

Research output: Contribution to journalArticle

Liu, Pingfang ; Burdzy, Artur ; Sowers, Lawrence. / Repair of the mutagenic DNA oxidation product, 5-formyluracil. In: DNA Repair. 2003 ; Vol. 2, No. 2. pp. 199-210.
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