Molecular and genetic effects of DNA base damages

DNA包含细胞的遗传信息。如果DNA受损，就会导致DNA复制或突变受阻。本研究从分子角度研究了碱基损伤引起的DNA微结构改变。得到的结果进一步与DNA聚合酶对遇到的碱基损伤的反应相关。结果总结如下：1。两种新的碱基损伤可能会导致DNA的微观结构改变。这些包括γ辐照产生的鸟嘌呤-丝氨酸加合物和一氧化氮产生的草胺苷。碱基位点广泛破坏DNA的稳定，导致双链DNA的局部熔化。-脱氧腺苷的热力学和结构效应取决于对链上的配对碱基。α -脱氧腺苷和碱基位点分别构成体内和体外DNA复制的中间和强阻断。前者只诱导单个核苷酸缺失，而后者产生碱基替换。DNA聚合酶对这些损伤的不同反应的分子机制可以用2中提到的损伤的热力学和结构效应来合理解释。

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.