Study of effect of cluster damage on recognition mechanism of 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). In general, these sites are repaired with less efficiency than single lesions. So far the detail mechanism of repair of multiple lesions is not known. A cluster damage containing a single strand break (SSB) within a few base pairs opposite to a 8-oxo-7,8-dihydroguanine (8oxoG) is one example of damage that is difficult to repair. In this study, we present results of molecular dynamics (MD) simulation of the models of complex of hOGG1 and cluster damaged DNA. Each model DNA contains two damages, SSB and 8oxoG. The separation of the location of the SSB from the 8oxoG on the opposite strand were +1bp, -1bp and -3bp, respectively. According to the observed results, the fluctuation of each damaged DNA was dependence on the separation between the two damages because the extent of contact with hOGG1 was different.