Molecular dynamics simulation of clustered DNA damage site including single strand brake

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

Ionizing radiation leads to clustered DNA damage sites. These sites are repaired with less efficiency than single lesions. So far the detail mechanism of repair of multiple lesions is not known. A lesion which locates within a few base pairs opposite to a 8oxo-G tends to inhibit excision of the 8oxo-G by repair enzyme MutM. The strength of inhibition effect is difference according to a kind of lesion. The inhibition effect of - single strand break (SSB) is stronger than that of SSB and abasic (AP) site. In this study, we present the results of molecular dynamics (MD) simulation, by comparing (1) - SSB, (2) SSB and (3) the AP site in cluster damaged DNA which is containing 8-oxoG. We discuss with the relation between the structural change of cluster damaged DNA and the inhibition effect.