The Study of the inhibition effect of clustered damage on repair 8oxoG by hOGG1

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 by hOGG1. 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 SSB and 8oxoG. According to the estimated binding free energy, the affinity between hOGG1 and the DNA including SSB located -3bp from 8oxoG was smaller than that between hOGG1 and the DNA including SSB located +3bp from 8oxoG. This result supported the relation between inhibition effects by cluster damaged DNA and affinity between damaged DNA and hOGG1.