Unrepairable DNA damage site composed of clustered lesions along ion particle tracks

Yokoya, Akinari; Shikazono, Naoya; Fujii, Kentaro; Ushigome, Takeshi*; Suzuki, Masao*; Urushibara, Ayumi; Watanabe, Ritsuko

It has been indicated that ion particle irradiation to living cells causes a clustered DNA damage site, defined as two or more lesions formed within a few nano meters, in a cell nuclei. The clustered damage is less readily repaired by enzymatic repair system so that it induces biological effects, such as mutation induction. We have studied the mechanism of clustered damage induction by biochemical approaches using closed circular plasmid DNA as a model molecule to be irradiated with He ions from TIARA. We have used base excision repair proteins as enzymatic probes to quantify base lesions. We have also applied a novel method using DNA denaturation to visualize multiple single strand breaks which hardly be detected by conventional method. Our recent results will be reported in this seminar.