Study of the binding between clustered damage DNA and hOGG1 by molecular dynamics simulation

Higuchi, Mariko; Pinak, M.

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 detail mechanism of repair of multiple lesions is not known. The experimental results showed that the excision of the 8-oxo-7,8-dihydroguanine (8oxoG) lesion by repair enzyme hOGG1 is strongly inhibited by the presence of a single strand break (SSB) on the opposite strand with a 1bp separation from the 8oxoG lesion and probability of repair increases with increasing distance between the SSB and the 8oxoG. In this study, we present results of molecular dynamics simulation of the models of complex of hOGG1 and cluster damaged DNA. Each model DNA contains two damages, SSB and 8oxoG. According to the observed results, the structural fluctuation of cluster damaged DNA decreased largely when hOGG1 bound the cluster DNA. The effect of the SSB located at -3bp was small because the residue located at -3bp did not contact directly with hOGG1.