Methylation of adenine bases at the N<sup>6</sup>H<sub>2</sub> groups decreases the melting temperature of the DNA duplex independently of the nucleotide sequence

Abstract

The effects of methylating adenine bases at the N6H2 groups on the thermal denaturation of the oligomer DNA duplexes were analyzed. Methylation of four adenine bases in a decamer DNA duplex decreased the melting temperature, Tm, by 9.4 degrees. Methylation of two adenine bases each in various dodecamer DNA duplexes decreased Tm by approximately 4 degrees. These effects correspond to destabilization of the duplexes by 0.6±0.1Kcal/mol per each methylation, and were essentially indepent of the length, the nucleotide sequence, and the number and positions of the methylated adenine bases incorporated. A possible biological function for methylation of adenine bases in destabilizing genomic DNA duplexes for the initiation of the DNA replication is discussed.