Introduction. Methods for the determination of nucleotide sequences in DNA have been perfected and an ever increasing number of DNA sequences have been determined. Research in molecular biology has now started to focus on the elucidation of the nature and functional significance of regulatory signals in DNA sequences. A simple and relatively easily recognized signal is that of methylated bases in DNA, although the function of these modifications on a molecular level is not yet understood. Methylated bases in DNA have been described by Hotchkiss (1948), Wyatt (1951) and Sinsheimer (1955). The base 5-methyl-cytosine was first crystallized in the Chemistry Department of Yale University by Johnson & Coghill (1925), who described 5-methyl-cytosine picrate. ‘This salt occurs in exceedingly minute, lath-like crystals. They possess a most brilliant luster and are a golden yellow’.

The DNA of prokaryotes contains the modified bases -methyl-adenine (6-mA) and 5-methyl-cytosine (5-mC); other modified bases have apparently not been found.


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