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Nonenzymatic methylation of DNA by the intracellular methyl group donor S‐adenosyl‐L‐methionine is a potentially mutagenic reaction.
Author(s) -
Rydberg B.,
Lindahl T.
Publication year - 1982
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1982.tb01149.x
Subject(s) - biology , methylation , dna methylation , methionine , dna , intracellular , methyl group , methyltransferase , group (periodic table) , biochemistry , genetics , microbiology and biotechnology , gene , gene expression , amino acid , chemistry , organic chemistry
Incubation of DNA with S‐adenosyl‐L‐methionine (SAM) in neutral aqueous solution leads to base modification, with formation of small amounts of 7‐methylguanine and 3‐methyladenine. The products have been identified by high performance liquid chromatography of DNA hydrolysates and by the selective release of free 3‐methyladenine from SAM‐treated DNA by a specific DNA glycosylase. We conclude that SAM acts as a weak DNA‐alkylating agent. Several control experiments including extensive purification of [3H‐methyl]SAM preparations and elimination of the alkylating activity by pretreatment of SAM with a phage T3‐induced SAM cleaving enzyme, have been performed to determine that the activity observed was due to SAM itself and not to a contaminating substance. We estimate that SAM, at an intracellular concentration of 4 X 10(‐5) M, causes DNA alkylation at a level similar to that expected from continuous exposure of cells to 2 X 10(‐8) M methyl methane‐sulphonate. This ability of SAM to act as a methyl donor in a nonenzymatic reaction could result in a background of mutagenesis and carcinogenesis. The data provide an explanation for the apparently universal occurrence of multiple DNA repair enzymes specific for methylation damage.