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Yokoya, Akinari; Shikazono, Naoya; Fujii, Kentaro
no journal, ,
In order to determine the yield of base lesions constituting the clustered lesion site, we have developed a novel technique by which irradiated DNA is analyzed after a denaturation-annealing treatment. The DNA including a clustered base lesion site is denatured to a single strand molecule, and then annealed with a new complementary strand. In the obtained double strand molecule, the clustered base lesion site would be resolved to isolated lesions which are able to be processed by enzymes. We will report the optimal condition of the denaturation-annealing treatment and present a result of preliminary experiment using X-irradiated DNA.
Higuchi, Mariko; Pinak, M.
no journal, ,
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 (8oxo-G) 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 the cluster damaged DNA. Each model DNA contains two damages as follows: (1) AP site and 8oxoG, (2) SSB and 8oxoG. The separation of the location of AP site and SSB from 8oxoG on the opposite strand were +1bp, -1bp and -3bp, respectively. According to the observed results, the structural deformation at the cluster depends on the relative positions of the AP site, or SSB, in respect to the 8-oxoG.