Molecular dynamics simulation of cluster damaged DNA and hOGG1

Higuchi, Mariko; Pinak, M.; Saito, Kimiaki  

Ionizing radiation leads to clustered DNA damage sites, which are defined as two or more single lesions induced within 10-20 base pairs (bp). The experimental results showed that the excision of the 8oxo-G lesion by repair enzyme hOGG1 is strongly inhibited by the presence of a SSB on the opposite strand with a 1bp separation from the 8oxo-G lesion. The detail mechanism of repair of multiple lesions is not known. In this study, we present the results of molecular dynamics simulation of hOGG1 and damaged DNA. We compare the result of single 8oxo-G DNA and hOGG1 complex and that of cluster damaged DNA. According to observed results, the structure of the DNA with SSB was stable with 8-oxoGs either flipped out or not. However in the DNA without SSB, the structure was stable only in the case of the 8-oxoG flip out.