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

被引：16
|
作者：
Bajinskis, Ainars [1 ,3 ]
Natarajan, Adayapalam T. [2 ]
Erixon, Klaus [1 ]
Harms-Ringdahl, Mats [1 ]
机构：
[1] Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Ctr Radiat Protect Res, SE-10691 Stockholm, Sweden
[2] Univ Tuscia, Dept Ecol & Biol Sci, I-01100 Viterbo, Italy
[3] Univ Latvia, Fac Med, LV-1586 Riga, Latvia
来源：
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS | 2013年 / 756卷 / 1-2期
关键词：
Indirect effect; Non-homologous end joining; Homologous recombination; High-LET radiation; RELATIVE BIOLOGICAL EFFECTIVENESS; BASE EXCISION-REPAIR; HAMSTER OVARY CELLS; IONIZING-RADIATION; MAMMALIAN-CELLS; CHO-CELLS; HUMAN FIBROBLASTS; CHROMATIN ORGANIZATION; SENSITIVE MUTANTS; GAMMA-RAYS;
D O I：
10.1016/j.mrgentox.2013.06.012
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
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 Cs-137 gamma-rays or radon progeny alpha-particles. Irradiation was also performed in the presence of 2 M 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 gamma-rays or alpha-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. (c) 2013 Elsevier BM. All rights reserved.
引用
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页码：21 / 29
页数：9
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