A possible model for the methylation of deoxycytidine in DNA

The modified base 5-methylcytidine has been found in the DNA of a number of different eukaryotic cells where it occurs principally in the dinucleotide sequence -CmpG- which is present as a palindrome in double-strand nucleic acid molecules. There is considerable evidence to indicate and suggest that 5-methylcytosine serves as a regulatory signal in eukaryotic gene expression. Replication of DNA containing -CmpG- gives rise to daughter DNA molecules containing new -CpG- dinucleotide sequences in which the cytidine residues are not methylated. Methylation of these residues is carried out by a methylase enzyme using S-adenosyl-L-methionine as a specific methyl group donor. The model discussed in the present communication tries to explain in chemical and biological terms the mechanism of the methylation reaction. The first reactions of the scheme are well known through the work of other investigators. However, we introduce a new concept into our reaction mechanism by postulating the direct involvement of S-adenosyl-L-methionine in the reaction through its covalent attachment to the cytosine ring followed by a specific ring closure and methylation involving transfer of a hydride ion. The model also gives a possible explanation of mechanism of interaction of dimethyl sulphoxide with the enzyme systems of certain eukaryotic cells, which are altered or changed in the regulation of gene expression by this chemical reagent.