Clustered DNA double-strand break formation and the repair pathway following heavy-ion irradiation. 2019

Yoshihiko Hagiwara, and Takahiro Oike, and Atsuko Niimi, and Motohiro Yamauchi, and Hiro Sato, and Siripan Limsirichaikul, and Kathryn D Held, and Takashi Nakano, and Atsushi Shibata
Department of Radiation Oncology, Gunma University, 3-39-22, Showa-machi, Maebashi, Gunma, Japan.

Photons, such as X- or γ-rays, induce DNA damage (distributed throughout the nucleus) as a result of low-density energy deposition. In contrast, particle irradiation with high linear energy transfer (LET) deposits high-density energy along the particle track. High-LET heavy-ion irradiation generates a greater number and more complex critical chromosomal aberrations, such as dicentrics and translocations, compared with X-ray or γ irradiation. In addition, the formation of >1000 bp deletions, which is rarely observed after X-ray irradiation, has been identified following high-LET heavy-ion irradiation. Previously, these chromosomal aberrations have been thought to be the result of misrepair of complex DNA lesions, defined as DNA damage through DNA double-strand breaks (DSBs) and single-strand breaks as well as base damage within 1-2 helical turns (<3-4 nm). However, because the scale of complex DNA lesions is less than a few nanometers, the large-scale chromosomal aberrations at a micrometer level cannot be simply explained by complex DNA lesions. Recently, we have demonstrated the existence of clustered DSBs along the particle track through the use of super-resolution microscopy. Furthermore, we have visualized high-level and frequent formation of DSBs at the chromosomal boundary following high-LET heavy-ion irradiation. In this review, we summarize the latest findings regarding the hallmarks of DNA damage structure and the repair pathway following heavy-ion irradiation. Furthermore, we discuss the mechanism through which high-LET heavy-ion irradiation may induce dicentrics, translocations and large deletions.

UI MeSH Term Description Entries
D002875 Chromosomes In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed) Chromosome
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D006657 Histones Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. Histone,Histone H1,Histone H1(s),Histone H2a,Histone H2b,Histone H3,Histone H3.3,Histone H4,Histone H5,Histone H7
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D053903 DNA Breaks, Double-Stranded Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently. Double-Stranded DNA Breaks,Double-Strand DNA Breaks,Double-Stranded DNA Break,Break, Double-Strand DNA,Break, Double-Stranded DNA,Breaks, Double-Strand DNA,Breaks, Double-Stranded DNA,DNA Break, Double-Strand,DNA Break, Double-Stranded,DNA Breaks, Double Stranded,DNA Breaks, Double-Strand,Double Strand DNA Breaks,Double Stranded DNA Break,Double Stranded DNA Breaks,Double-Strand DNA Break
D057170 Translational Research, Biomedical The endeavour to traverse a specific step of the translation process of turning an observation in the laboratory, clinic, or community into an intervention that will improve the health of individuals and the public. (from Nat Rev Drug Discov. 2018 July ; 17(7): 455–456.) Translational Medical Research,Translational Research,Translational Research, Medical,Biomedical Translational Research,Medical Research, Translational,Medical Translational Research,Research, Biomedical Translational,Research, Medical Translational,Research, Translational,Research, Translational Medical
D020450 Heavy Ions Positively-charged atomic nuclei that have been stripped of their electrons. These particles have one or more units of electric charge and a mass exceeding that of the Helium-4 nucleus (alpha particle). Ions, Heavy,Heavy Ion,Ion, Heavy

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