The Affinity of close-two-damaged DNA and repair enzyme 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 complex of hOGG1 and cluster damaged DNA. We prepared the several damaged DNA models which are varied relative location between the SSB and the 8oxoG. According to the estimated binding free energy, the affinity between hOGG1 and the damaged DNA was qualitatively compatible with the probability of excision of 8oxoG by hOGG1. This result supported the relation between inhibition effects by cluster damaged DNA.