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J. Biol. Chem., Vol. 276, Issue 24, 21821-21827, June 15, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/24/21821    most recent M100998200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Speina, E. Articles by Tudek, B. Search for Related Content PubMed PubMed Citation Articles by Speina, E. Articles by Tudek, B.

The Pyrimidine Ring-opened Derivative of 1,N⁶-Ethenoadenine Is Excised from DNA by the Escherichia coli Fpg and Nth Proteins^*,

Elbieta Speina, Jarosaw M. Ciela, Jacek Wójcik, Monika Bajek, Jarosaw T. Kumierek, and Barbara Tudek

From the Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawiskiego 5A, 02-106 Warsaw, Poland

It was previously shown that 1,N⁶-ethenoadenine (A) in DNA rearranges into a pyrimidine ring-opened derivative of 20-fold higher mutagenic potency in Escherichia coli (AB1157 lacU169) than the parental A (Basu, A. K., Wood, M. L., Niedernhofer, L. J., Ramos, L. A., and Essigmann, J. M. (1993) Biochemistry 32, 12793-12801). We have found that at pH 7.0, the stability of the N-glycosidic bond in dA is 20-fold lower than in dA. In alkaline conditions, but also at neutrality, dA depurinates or converts into products: dA  B  C  D. Compound B is a product of water molecule addition to the C(2)-N(3) bond, which is in equilibrium with a product of N(1)-C(2) bond rupture in dA. Compound C is a deformylated derivative of ring-opened compound B, which further depurinates yielding compound D. Ethenoadenine degradation products are not recognized by human N-alkylpurine-DNA glycosylase, which repairs A. Product B is excised from oligodeoxynucleotides by E. coli formamidopyrimidine-DNA glycosylase (Fpg) and endonuclease III (Nth). Repair by the Fpg protein is as efficient as that of 7,8-dihydro-8-oxoguanine when the excised base is paired with dT and dC but is less favorable when paired with dG and dA. Ethenoadenine rearrangement products are formed in oligodeoxynucleotides also at neutral pH at the rate of about 2-3% per week at 37 °C, and therefore they may contribute to A mutations.

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