Significance of strand break repair in determining the mutagenic potential of clustered DNA damage

クラスターDNA損傷による突然変異生成における鎖切断修復の重要性

鹿園 直哉; 野口 実穂; 漆原 あゆみ; O'Neill, P.*; 横谷 明徳

Shikazono, Naoya; Noguchi, Miho; Urushibara, Ayumi; O'Neill, P.*; Yokoya, Akinari

Clustered DNA damage, defined as two or more lesions within one to two helical turns of DNA induced by a single radiation track, is a unique feature of ionizing radiation. To examine the role of strand break repair in mutation induction, the clustered single strand break (SSB) + 8-oxo-7,8-dihydroguanine (8-oxoG) lesions were transfected in the strain of , which lacks Pol I that participates in repair synthesis. We found that the mutation frequencies of SSB + 8-oxoG lesions become markedly higher in the strain than those in strain, while the mutation frequencies of single lesions remained low in . These results indicate that Pol I plays an important role in protecting against mutation and suggest that the extent of strand break repair determines the mutagenic potential of bi-stranded clustered DNA damage containing base lesions.