Theoretical Study Of Methylation Mechanism On DNA Bases

The double-helical DNA is a very important intermediate in storing and transferring genetic informations. The high fidelity of DNA replication is guaranteed by the high specificity of nucleic acid(NA) base pairing in DNA. So the integrity of bases pairing must be kept during the DNA replication. But inherent and extrinsic factors of organism would influence the normal base pairs in the course of DNA replication, causing the base mispairing and DNA replication errors.G:C and A:T Watson-Crick base pairs and non-Watson-Crick base pairs are coexist in organism. Not considering others influence, there are still several possible mispairing such as G:T and G:U, and so on, which often occur in DNA replication. Although a minority of mispairing may has some biological functions, for instance, G:U mispairing can make the structures of Group I introns easily to form and stabilize the transition state through Mg²⁺, the majority of mispairing would block DNA replication.Many extrinsic factors such as alkylating can bring lesions to DNA base pairs, the alkylating destroy the normal base pairing or interaction between bases and proteins by connecting to NA bases. These lesions would lead to some sicks or even cancer if they would not be repaired in time. Experimental studies suggest that some manual repaired enzymes will repair those lesions. So, it is very significant to exploring the mechanism of alkylating to help to the development of man-made enzymes and some medicines.In the paper, ab initio quantum chemical was used to studying the methylating of NA bases in detailed. On the discussion about mechanism of mutation of methylating, we explored thermodynamics and dynamic properties on base pairs, investigating the proton transfer on base pairs. And we also research the impact of methylating on hydrogen bond and stacked bond in base pairs under considering water molecules.The rusults show that methylating can make the proton transfering in base pairs easily happened, changing the distribution of charges or the mode of pairing. Tautomers of bases would also interact with methylating, resulting in the stabilization of tautomers. The results also indicate that methylating would change the interaction among base pairs, altering the stabilizaton ofstructures and leading to DNA replication error, consequently.