DNA double strand breaks induced by the indirect effect of radiation are more efficiently repaired by non-homologous end joining compared to homologous recombination repair

• Published in: Mutation research. Genetic toxicology and environmental mutagenesis 2013-08, Vol.756 (1-2), p.21-29
• Main Authors: Bajinskis, Ainars, Natarajan, Adayapalam T., Erixon, Klaus, Harms-Ringdahl, Mats
• Format: Article
• Language: English
• Subjects: Cellular biology; DNA damage; DNA repair; High-LET radiation; Homologous recombination; Indirect effect; Molecular biology; Non-homologous end joining; Radiation
• ISSN: 1383-5718; 1879-3592; 1879-3592
• DOI: 10.1016/j.mrgentox.2013.06.012

•The indirect effect of γ-radiation contributes significantly to the clonogenic survival and yields of MN.•NHEJ and BER work on DNA lesions originating from the indirect effect of low-LET radiation.•The indirect effect of radiation acts preferentially on the open chromatin structure. The aim of this study was to investigate the relative involvement of three major DNA repair pathways, i.e., non-homologous end joining (NHEJ), homologous recombination (HRR) and base excision (BER) in repair of DNA lesions of different complexity induced by low- or high-LET radiation with emphasis on the contribution of the indirect effect of radiation for these radiation qualities. A panel of DNA repair-deficient CHO cell lines was irradiated by 137Cs γ-rays or radon progeny α-particles. Irradiation was also performed in the presence of 2M DMSO to reduce the indirect effect of radiation and the complexity of the DNA damage formed. Clonogenic survival and micronucleus assays were used to estimate efficiencies of the different repair pathways for DNA damages produced by direct and indirect effects. Removal of the indirect effect of low-LET radiation by DMSO increased clonogenic survival and decreased MN formation for all cell lines investigated. A direct contribution of the indirect effect of radiation to DNA base damage was suggested by the significant protection by DMSO seen for the BER deficient cell line. Lesions formed by the indirect effect are more readily repaired by the NHEJ pathway than by HRR after irradiation with γ-rays or α-particles as evaluated by cell survival and the yields of MN. The results obtained with BER- and NHEJ-deficient cells suggest that the indirect effect of radiation contributes significantly to the formation of repair substrates for these pathways.