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

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 ${it mutYpolA}$ strain of ${it E. coli}$, 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 ${it mutYpolA}$ strain than those in ${it mutY}$ strain, while the mutation frequencies of single lesions remained low in ${it mutYpolA}$. 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.

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