Shikazono Naoya, Akamatsu Ken
Department of Quantum life Science, Quantum Beam Science Research Directorate, National Institutes of Quantum and Radiological Science and Technology, 8-1-7 Umemidai, Kizugawa-shi, Kyoto, 619-0215 Japan.
Mutat Res. 2018 Jul;810:6-12. doi: 10.1016/j.mrfmmm.2018.05.001. Epub 2018 May 26.
Ionizing radiation causes various different types of DNA damage. If not repaired, DNA damage can have detrimental effects. Previous studies indicate that the spatial distribution of DNA lesions induced by ionizing radiation is highly relevant to the ensuing biological effects. Clustered DNA damage, consisting of DNA lesions in close proximity, has been studied in detail, and has enhanced mutagenic potential depending on the configuration of the lesions. However, it is not known whether clustered DNA damage affects the mutagenic potential of a sufficiently separated, isolated lesion. Using synthetic damage constructs, we investigated the mutagenic potential of an isolated 8-oxo-7,8-dihydroguanine (8-oxoG) separated by at least 7 bp from other lesions. Under the spatial distribution of DNA lesions tested in the present study, neighboring clustered DNA lesions likely retarded the processing of the isolated 8-oxoG and resulted in enhanced mutation frequency. However, the enhanced mutagenic potential was dependent on which strand the isolated 8-oxoG was located. Our results indicate that the processing of a bi-stranded cluster could affect the mutagenic outcome of a nearby isolated lesion, separated up to ∼20 bp.
电离辐射会导致多种不同类型的DNA损伤。若不进行修复，DNA损伤可能会产生有害影响。先前的研究表明，电离辐射诱导的DNA损伤的空间分布与随后的生物学效应高度相关。由紧密相邻的DNA损伤组成的簇状DNA损伤已得到详细研究，并且根据损伤的构型具有增强的诱变潜力。然而，尚不清楚簇状DNA损伤是否会影响充分分离的孤立损伤的诱变潜力。我们使用合成损伤构建体，研究了与其他损伤至少相隔7个碱基对的孤立的8-氧代-7,8-二氢鸟嘌呤（8-氧代鸟嘌呤，8-oxoG）的诱变潜力。在本研究测试的DNA损伤的空间分布下，相邻的簇状DNA损伤可能会阻碍孤立的8-氧代鸟嘌呤的处理，并导致突变频率增加。然而，诱变潜力的增强取决于孤立的8-氧代鸟嘌呤位于哪条链上。我们的结果表明，双链簇的处理可能会影响附近相隔达约20个碱基对的孤立损伤的诱变结果。
