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PMID:3856245

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Citation

Farrance, IK and Ivarie, R (1985) Ethylation of poly(dC-dG).poly(dC-dG) by ethyl methanesulfonate stimulates the activity of mammalian DNA methyltransferase in vitro. Proc. Natl. Acad. Sci. U.S.A. 82:1045-9

Abstract

Ethylation of poly(dC-dG).poly(dC-dG) with ethyl methanesulfonate (EtMes), a known carcinogen, at increasing molar ratios of EtMes/C X 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.

Links

PubMed PMC397190

Keywords

Animals; DNA (Cytosine-5-)-Methyltransferase/metabolism; Ethyl Methanesulfonate/pharmacology; Methyltransferases/metabolism; Models, Molecular; Polydeoxyribonucleotides; Rats; Substrate Specificity

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:DNMT1

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:DNMT1

involved_in

GO:0010424: DNA methylation on cytosine within a CG sequence

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:DNMT1

involved_in

GO:0046500: S-adenosylmethionine metabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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