Increased sensitivity to sparsely ionizing radiation due to excessive base excision in clustered DNA damage sites in Escherichia coli

抄録

Purpose: To clarify the cellular processing and repair mechanisms for radiation-induced clustered DNA damage, we examined the correlation between the levels of DNA glycosylases and the sensitivity to ionizing radiation in Escherichia coli.
Materials and methods: The survival of gamma-rays, X-rays, alpha-particles and H₂O₂ were determined in E. coli with different levels of DNA glycosylases. DSB formation by post-irradiation treatment with DNA glycosylases was assayed with gamma-irradiated plasmid DNA in vitro.
Results/Conclusion: An E. coli mutM nth nei triple mutant was less sensitive to low-LET radiation (gamma-rays and X-rays) than the wild-type strain. Overproduction of E. coli MutM, Nth, Nei and human OGG1 increased the sensitivity to gamma-rays, whereas it did not affect the sensitivity to alpha-particles. Treatment of gamma-irradiated plasmid DNA with MutM protein converted the supercoiled to the linear form of the DNA. On the other hand, overproduction of MutM conferred resistance to H₂O₂ on the E. coli mutM nth nei mutant. The levels of DNA glycosylases affect the sensitivity of E. coli to low-LET radiation. Excision by DNA glycosylases converts nearly opposite base lesions in clustered damage to DSBs which are potentially lethal. Post-irradiation treatment of H₂O₂ increased the probability of clustered damage formation.