Mechanism of cluster DNA damage repair in response to high-atomic number and energy particles radiation.
Low-linear energy transfer (LET) radiation (i.e., γ- and X-rays) induces DNA double-strand breaks (DSBs) that are rapidly repaired (rejoined). In contrast, DNA damage induced by the dense ionizing track of high-atomic number and energy (HZE) particles is slowly repaired or is irreparable. These unrepaired and/or misrepaired DNA lesions may contribute to the observed higher relative biological effectiveness for cell killing, chromosomal aberrations, mutagenesis, and carcinogenesis in HZE particle irradiated cells compared to those treated with low-LET radiation. The types of DNA lesions induced by HZE particles have been characterized in vitro and usually consist of two or more closely spaced strand breaks, abasic sites, or oxidized bases on opposing strands. It is unclear why these lesions are difficult to repair. In this review, we highlight the potential of a new technology allowing direct visualization of different types of DNA lesions in human cells and document the emerging significance of live-cell imaging for elucidation of the spatio-temporal characterization of complex DNA damage. We focus on the recent insights into the molecular pathways that participate in the repair of HZE particle-induced DSBs. We also discuss recent advances in our understanding of how different end-processing nucleases aid in repair of DSBs with complicated ends generated by HZE particles. Understanding the mechanism underlying the repair of DNA damage induced by HZE particles will have important implications for estimating the risks to human health associated with HZE particle exposure.
Division of Molecular Radiation Biology, Department of Radiation Oncology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, United States. Aroumougame.Asaithamy@UTsouthwestern.edu
Aroumougame
A
Asaithamby
David J
DJ
Chen
D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins; D003851:Deoxyribonucleases; D004720:Endonucleases; D005090:Exodeoxyribonucleases / Q000502:physiology; D006801:Humans; D007118:Immunoassay; D018499:Linear Energy Transfer; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000378:metabolism; D053484:RecQ Helicases / Q000502:physiology; D000071657:Werner Syndrome Helicase
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D004247:DNA; C426344:DCLRE1C protein, human; D003851:Deoxyribonucleases; D004720:Endonucleases; D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase