Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 366, Issue 3, Pages 752-757Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2007.12.010
Keywords
DNA repair; oxidative DNA damage; base-pair mismatch; hydroxy uracil
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Funding
- NCI NIH HHS [CA10227] Funding Source: Medline
- NIAID NIH HHS [U01 AI054827] Funding Source: Medline
- NIEHS NIH HHS [P30 ES006676-13, ES06676, P30 ES006676] Funding Source: Medline
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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 ill 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 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. (c) 2007 Elsevier Inc. All rights reserved.
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