HYDRATION AND RECOGNITION OF METHYLATED CPG STEPS IN DNA

The analysis of the hydration pattern around methylated CpG steps in t hree high resolution (1.7, 2.15 and 2.2 Angstrom) crystal structures o f A-DNA decamers reveals that the methyl groups of cytosine residues a re well hydrated, In comparing the native structure with two structura lly distinct forms of the decamer d(CCGCCGGCGG) fully methylated at it s CpG steps, this study shows also that in certain structural and sequ ence contexts, the methylated cytosine base can be more hydrated that the unmodified one. These water molecules seem to be stabilized in fro nt of the methyl group through the formation C-H ... O interactions. I n addition, these structures provide the first observation of magnesiu m cations bound to the major groove of A-DNA and reveal two distinct m odes of metal binding in methylated and native duplexes. These finding s suggest that methylated cytosine bases could be recognized by protei n or DNA polar residues through their tightly bound water molecules.