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Mammalian DNA methylation and a nuclear S ‐adenosyl L‐methionine‐dependent nuclease activity
Author(s) -
Cato Andrew C.B.,
Burdon Roy H.
Publication year - 1979
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(79)80242-2
Subject(s) - citation , methylation , methionine , chemistry , philosophy , stereochemistry , microbiology and biotechnology , dna , library science , biology , biochemistry , computer science , amino acid
Studies on bacteriophage-cell interactions have revealed that bacterial cells contain ‘restriction’ nucleases which recognise a specific sequence of nucleotides within DNA and make a double-stranded endonucleolytic cleavage at the sequence, or elsewhere in the DNA. On the other hand ‘modification’ enzymes also exist in these cells which can recognise the same nucleotide sequence but modify it so as to prevent its cleavage [l-6]. The bacterial restriction enzymes can be divided into two classes. Class I-type enzymes require ATP, magnesium ions and S-adenosyl L-methionine (SAM) as cofactors and the products of cleavage are heterogeneous. Class II-type enzymes require only Mg*’ but give rise to discrete fragments of DNA. The phenomenon of ‘modification’ is also encountered in eukaryotes. In mammals most of the modification of DNA cytosine residues occurs shortly after DNA synthesis [7] and most of the methylated sequences occur in the sequence m’CG, but the distribution of bases on either side of this dinucleotide sequence appears random [8,9]. As yet there has been little positive data to indicate a biological role for DNA modification in mammalian cells. We explore here the possibility that the modification of certain C-G sequences protects DNA from the nucleolytic effects of SAM-dependent deoxyribonucleases, which appear to occur in nuclei of cultured baby hamster kidney fibroblasts (BHK-21 cells). 2. Experimental