In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 96, No. 12 ( 1999-06-08), p. 6615-6620
Abstract:
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 C GCGAT) duplexes, M 1 G 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 M 1 G 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 M 1 G 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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.96.12.6615
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
1999
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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