Base-pairing properties of the oxidized cytosine derivative, 5-hydroxy uracil

Varatharasa Thiviyanathan, Anoma Somasunderam, David E. Volk, Tapas Hazra, Sankar Mitra, David G. Gorenstein

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The most abundant base-substitution mutation resulting from oxidative damage to DNA is the GC to AT transition mutation. 5-hydroxyuracil (5-OHU), produced by the oxidative deamination of cystosine, has been established as the major chemical precursor for this most abundant transition mutation. Results from NMR spectroscopy and UV melting experiments show that 5-OHU would form the most stable pair with G, and the least stable pair with C. The hydroxyl group in the 5th position of the 5-OHU residue may play a role in increasing the stability of the 5-OHU:G pair over the normal Watson-Crick pair, the 5-OHU:A. The 5-OHU:C base pair would be least stable, and would destabilize the base-stacking in the duplex. Our results explain why certain DNA polymerases preferentially incorporate G opposite to 5-OHU over A and why C does not get incorporated against 5-OHU during DNA replication in vivo.

Original languageEnglish (US)
Pages (from-to)752-757
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume366
Issue number3
DOIs
StatePublished - Feb 15 2008
Externally publishedYes

Fingerprint

Uracil
Cytosine
Base Pairing
Derivatives
Mutation
DNA
DNA-Directed DNA Polymerase
Hydroxyl Radical
Nuclear magnetic resonance spectroscopy
Deamination
Melting
Substitution reactions
DNA Replication
Freezing
DNA Damage
Magnetic Resonance Spectroscopy
Experiments
5-hydroxyuracil

Keywords

  • Base-pair mismatch
  • DNA repair
  • Hydroxy uracil
  • Oxidative DNA damage

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Base-pairing properties of the oxidized cytosine derivative, 5-hydroxy uracil. / Thiviyanathan, Varatharasa; Somasunderam, Anoma; Volk, David E.; Hazra, Tapas; Mitra, Sankar; Gorenstein, David G.

In: Biochemical and Biophysical Research Communications, Vol. 366, No. 3, 15.02.2008, p. 752-757.

Research output: Contribution to journalArticle

Thiviyanathan, Varatharasa ; Somasunderam, Anoma ; Volk, David E. ; Hazra, Tapas ; Mitra, Sankar ; Gorenstein, David G. / Base-pairing properties of the oxidized cytosine derivative, 5-hydroxy uracil. In: Biochemical and Biophysical Research Communications. 2008 ; Vol. 366, No. 3. pp. 752-757.
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AU - Gorenstein, David G.

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AB - The most abundant base-substitution mutation resulting from oxidative damage to DNA is the GC to AT transition mutation. 5-hydroxyuracil (5-OHU), produced by the oxidative deamination of cystosine, has been established as the major chemical precursor for this most abundant transition mutation. Results from NMR spectroscopy and UV melting experiments show that 5-OHU would form the most stable pair with G, and the least stable pair with C. The hydroxyl group in the 5th position of the 5-OHU residue may play a role in increasing the stability of the 5-OHU:G pair over the normal Watson-Crick pair, the 5-OHU:A. The 5-OHU:C base pair would be least stable, and would destabilize the base-stacking in the duplex. Our results explain why certain DNA polymerases preferentially incorporate G opposite to 5-OHU over A and why C does not get incorporated against 5-OHU during DNA replication in vivo.

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