Imidazole open ring 7-methylguanine: an inhibitor of DNA synthesis |
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Authors: | S Boiteux J Laval |
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Affiliation: | Unite de Biochimie et Enzymologie Institut G. Roussy, 94805 Villejuif Cedex, France |
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Abstract: | Guanine methylated at the N7 position (me7G) is susceptible to cleavage of the imidazole ring yielding: 2,6-diamino-4-hydroxy-5N-methyl-formamidopyrimidine (rom7G). DNA synthesis catalysed by E.coli DNA polymerase I, using as templates poly(dGC) containing either me7G or rom7G, show that rom7G blocks DNA chain elongation. It implies a potential killing effect. Furthermore rom7G does not induce mispairing with either dAMP or dTMP. me7G does not affect DNA synthesis. The results suggest that, beside AP-sites, rom7G is a potential killing lesion in cells treated by alkylating agents. |
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Keywords: | G 2 6-diamino-4-hydroxy-5N-methyl-formamidopyrimidine DMS dimethyl sulfate |
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