Base-pairing properties of the oxidized cytosine derivative, 5-hydroxy uracil.
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.
Thiviyanathan
Varatharasa
V
Sealy Center for Structural Biology & Molecular Biophysics, Sealy Center for Molecular Sciences, Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Somasunderam
Anoma
A
Volk
David E
DE
Hazra
Tapas K
TK
Mitra
Sankar
S
Gorenstein
David G
DG
D020029:Base Pairing; D003198:Computer Simulation; D003596:Cytosine / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D010084:Oxidation-Reduction; D014498:Uracil / Q000031:analogs & derivatives* / Q000737:chemistry
C045975:5-hydroxyuracil; D014498:Uracil; D003596:Cytosine; D004247:DNA