Duplex DNA catalyzes the chemical rearrangement of a malondialdehyde deoxyguanosine adduct

• DOI: 10.1073/pnas.96.12.6615
• Publication Date: 2002-07-26T14:39:15Z
• Authors: Hui Mao; Nathalie C. Schne...; Jason P. Weisenseel; Lawrence J. Marnett; Michael P. Stone
• Keywords: Deoxyguanosine; Propenyl; DNA adduct; Cytosine

The primary DNA lesion induced by malondialdehyde, a byproduct of lipid peroxidation and prostaglandin synthesis, is 3-(2′-deoxy-β- d -erythro-pentofuranosyl)-pyrimido[1,2-a]purin-10(3H)-one (M 1 G). When placed opposite cytosine (underlined) at neutral pH in either the d(GGTMTCCG)⋅d(CGGA C ACC) or d(ATCGCMCGGCATG)⋅ d(CATGCCG GCGAT) duplexes, M G spontaneously quantitatively converts to ring-opened derivative N 2 -(3-oxo-1-propenyl)-dG. Ring-opening reversible on thermal denaturation. does not occur single-stranded oligodeoxynucleotides when T duplex. presence complementary required stabilize -(3-oxo-1-propenyl)-dG duplex pH. thymine duplex, it revert G. A mechanism for conversion proposed which exocyclic amino group attacks C8 position ring facilitates opening via formation transient Schiff base. Addition water base regenerates catalytic generates These results document ability catalyze transformation one adduct into another, may have important consequences mutagenesis repair.