Methylation of DNA by three N-nitroso compounds: evidence for sequence specific methylation by a common intermediate |
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Authors: | J R Milligan S Hirani-Hojatti L Catz-Biro M C Archer |
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Institution: | Department of Medical Biophysics, University of Toronto, Ontario, Canada. |
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Abstract: | Methylation in vitro of calf thymus DNA, a supercoiled plasmid, poly(dG).poly(dC), and poly(dGdC).poly(dGdC) by N-nitroso(acetoxy-methyl)methylamine and N-nitroso(acetoxybenzyl)methylamine in the presence of esterase, and by N-nitrosomethylurea was investigated. Although there were differences in the amounts of 7-methylguanine and O6-methylguanine formed in the various DNA substrates, the methylation pattern was the same for each of these methylating agents. The three compounds reacted identically when methylation of a portion of a 345 bp restriction fragment of the plasmid pBR322 was examined at nucleotide resolution by a sequencing assay. They also showed a tendency to react preferentially with particular guanines. These data suggest that the three N-nitroso compounds methylate DNA via a common intermediate such as the methyl diazonium ion, which exhibits some sequence specificity. |
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