Molecular and genetic effects of DNA base damages

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DNA contains the genetic information of cells. If DNA is damaged, this results in arrest of DNA replication or mutation. In this study, molecular aspects of the alteration of DNA microstructures induced by base damages have been studied. The obtained results are further correlated with the response of DNA polymerases to the encountered base damages. The results are summarized as follows.1.Two novel base damages that potentially introduce microstructural alteration into DNA have been identified. These include a guanine-serine adduct produced by gamma-irradiation, and oxanosine produced by nitric oxide.2.Abasic sites extensively destabilize DNA resulting in local melting of duplex DNA.The thermodynamic and structural effects of alpha-deoxyadenosine depend on the paired base in the opposite strand.3.alpha-Deoxyadenosine and abasic sites constitute intermediate and strong blocks to DNA replication, respectively, in vivo as well as in vitro. The former induces a single nucleotide deletion exclusively, while the latter generates base substitutions. The molecular mechanism of the differential responses of DNA polymerase to these damages can be reasonably explained by the thermodynamic and structural effects of the damages mentioned in 2.