Imidazole open ring 7-methylguanine: an inhibitor of DNA synthesis.
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.
D002384:Catalysis; D004247:DNA / Q000096:biosynthesis*; D004256:DNA Polymerase I / Q000378:metabolism*; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D007093:Imidazoles / Q000378:metabolism*; D011089:Polydeoxyribonucleotides / Q000378:metabolism; D013698:Templates, Genetic
D007093:Imidazoles; D011089:Polydeoxyribonucleotides; C019530:poly(dC-dG); D006147:Guanine; C008450:7-methylguanine; D004247:DNA; D004256:DNA Polymerase I; D004259:DNA-Directed DNA Polymerase