REPAIR OF OXIDATIVE MODIFICATIONS OF DNA - THE CASE OF 5-METHYLCYTOSINE IN DNA

5-Methylcytosine is a minor component of the DNA of mammals and other higher eukaryotic organisms. It appears to play an important role in t he control of gene expression and in other physiological processes. Bo th somatic mutations and germ line mutations appear to take place pref erentially at sites of 5-methylcytosine residues. We have been studyin g the products formed from methylcytosine residues which can be produc ed by radiation and by oxidative stresses. We have also been studying the pathways by which such products can be repaired. Three classes of modifications to methylcytosine are being characterized: (i) lesions r esulting from oxidation of the methyl group, (ii) lesions resulting fr om deamination, and (iii) lesions resulting from photohydration of the 5,6-ethylenic bond. Several interrelated base excision repair pathway s appear to have developed to respond to these lesions. Our current st udies are designed to evaluate the relative importance of these lesion s and the corresponding repair pathways in mammalian cells.