CARB 19 |
| Oxidation of deoxyribose in DNA by radical-mediated DNA-damaging drugs and agents produces a wide range of lesions, with a different spectrum of products for each position in the sugar. Recent studies from our group have revealed novel features of the chemistry of deoxyribose oxidation, as well as insights into the biological consequences of the damage. In addition to the generation of strand breaks and abasic sites that both require repair and are able to inhibit DNA repair enzymes, the electrophilic products of deoxyribose oxidation can react with DNA and proteins to form stable adduct species. Examples of these adducts include the mutagenic M1G adduct derived from base propenal arising from 4'-oxidation of deoxyribose, and the N6-formyllysine adduct in histone proteins, which arises from the 3'-formylphosphate residue of 5'-chemistry and is a chemical analog of acetylated lysine important in controlling gene expression. These studies reveal that deoxyribose oxidation causes more than just strand breaks. |
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Nucleic Acids as Drug Targets
8:00 AM-11:50 AM, Monday, August 20, 2007 BCEC -- 208, Oral
Division of Carbohydrate Chemistry |