Duplex DNA catalyzes the chemical rearrangement of a malondialdehyde deoxyguanosine adduct

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