Low-Energy (5–20 eV) Electron-Induced Single and Double Strand Breaks in Well-Defined DNA Sequences

Abstract

Ionizing radiation is used in cancer radiation therapy to effectively damage the DNA of tumors. The main damage is due to generation of highly reactive secondary species such as low-energy electrons (LEEs). The accurate quantification of DNA radiation damage of well-defined DNA target sequences in terms of absolute cross sections for LEE-induced DNA strand breaks is possible by the DNA origami technique; however, to date, it is possible only for DNA single strands. In the present work DNA double strand breaks in the DNA sequence 5′-d(CAC) 4 /5′-d(GTG) 4 are compared with DNA single strand breaks in the oligonucleotides 5′-d(CAC) 4 and 5′-d(GTG) 4 upon irradiation with LEEs in the energy range from 5 to 20 eV. A maximum of strand break cross section was found around 7 and 10 eV independent of the DNA sequence, indicating that dissociative electron attachment is the underlying mechanism of strand breakage and confirming previous studies using plasmid DNA.

Observation of Transient Anions That Do Not Decay through Dissociative Electron Attachment: New Pathways for Radiosensitization

“…Furthermore, neutral dissociation events are expected to be even more chemically relevant than DEA events breaking a single bond, because two radical species (and a released electron) are produced in the former, against only one radical in the latter. While DEA is believed to make a major contribution to the understanding of radiosensitivity, − our results point out neutral dissociation through catalytic electrons as a new pathway for radiosensitization. In particular, this pathway represents an alternative radiosensitizing mechanism for nitroimidazolic radiosensitizers, which could play a role similarly important to that of the previously proposed associative attachment (for nimorazole and metronidazole) and DEA (for smaller NIs − ) electron-induced processes.…”

“…The role of electron-induced chemistry is increasingly recognized within the context of radiosensitization, − although it is a prevalent mechanism in discharges, plasma processing, and nanolithography, among many others. − The efficacy of radiotherapy treatments can be significantly improved when deployed in conjunction with radiosensitizer compounds. − These molecules act by enhancing the radiosensitivity of tumor tissues and/or cells, thus allowing the delivered doses to be reduced, while minimizing the damage induced by radiotherapy in the neighboring healthy tissues. Although the underlying mechanisms of radiosensitivity remain poorly understood, the production and subsequent chemistry mediated by free radicals certainly play a key role. , In particular, low-energy electrons (<10 eV), generated in large numbers along the track of the primary ionization radiation, , can efficiently produce free radicals via DEA processes .…”

Lab-on-a-DNA origami: nanoengineered single-molecule platforms

“…7A . 93 Triangular DNA origami structures are mainly used because they are the stiffest 2D DNA origami structure that does not tend to form aggregates. 94 The target DNA structures are extended from staple strands of the DNA origami and are labeled with biotin.…”

Lethal and Non-Lethal Functions of Caspases in the DNA Damage Response

“…DSBs arise from both endogenous and exogenous sources, such as free radicals and ionizing radiation, respectively [ 7 , 8 ], as well as V(D)J recombination and class switch recombination (CSR) [ 9 , 10 ]. SSBs can be induced by ionizing radiation, reactive oxygen species (ROS), and as a result of replication errors resulting in single strand DNA (ssDNA) [ 11 , 12 ]. Both types of breaks are detected and bound by polyADP-ribose polymerase 1 (PARP1), which repairs the DNA [ 13 ].…”