Ethylation of poly(dC-dG)· poly(dC-dG) by Ethyl Methanesulfonate Stimulates the Activity of Mammalian DNA Methyltransferase in vitro

Ethylation of poly(dC-dG)· poly(dC-dG) with ethyl methanesulfonate (EtMes), a known carcinogen, at increasing molar ratios of EtMes/C· G base pairs progressively stimulated the methyl-accepting ability of the DNA during in vitro methylation by partially purified rat DNA (cytosine-5)-methyltransferas...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1985-02, Vol.82 (4), p.1045-1049
Main Authors: Farrance, Iain K., Ivarie, Robert
Format: Article
Language:English
Subjects:
Animals
Biochemistry
Biological and medical sciences
Copolymers
Deoxyribonucleosides
DNA
DNA (Cytosine-5-)-Methyltransferases - metabolism
Enzymes
Ethyl Methanesulfonate - pharmacology
Fundamental and applied biological sciences. Psychology
Gene expression
In Vitro Techniques
Mesylates
Methylation
Methyltransferases - metabolism
Models, Molecular
Molecular and cellular biology
Molecular genetics
Nucleic acids
Polydeoxyribonucleotides
Quaternary ammonium compounds
Rats
Somatic cells
Substrate Specificity
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Summary:Ethylation of poly(dC-dG)· poly(dC-dG) with ethyl methanesulfonate (EtMes), a known carcinogen, at increasing molar ratios of EtMes/C· G base pairs progressively stimulated the methyl-accepting ability of the DNA during in vitro methylation by partially purified rat DNA (cytosine-5)-methyltransferase (EC 2.1.1.37). Maximum stimulation was 2-fold over mock-treated DNA when 2.7% of the guanines were modified at the N-7 position, the major site of ethylation by EtMes in DNA. If a CpG site ``hemiethylated'' at guanine N-7 mimics a hemimethylated CpG site, we calculate that the enzyme has a relative affinity for hemiethylated CpG 18-fold above unmodified CpG. If ethylation of a dioxyphosphate oxygen of the phosphodiester bond is responsible for stimulation, the relative affinity could be much higher, up to 370-fold.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.82.4.1045