Publicação
Unraveling the Complexity of DNA Radiation Damage Using DNA Nanotechnology
| dc.contributor.author | Ameixa, João | |
| dc.contributor.author | Bald, Ilko | |
| dc.contributor.institution | CeFITec – Centro de Física e Investigação Tecnológica | |
| dc.contributor.institution | DF – Departamento de Física | |
| dc.contributor.pbl | ACS - American Chemical Society | |
| dc.date.accessioned | 2024-09-29T22:22:02Z | |
| dc.date.available | 2024-09-29T22:22:02Z | |
| dc.date.issued | 2024-06-04 | |
| dc.description | Funding Information: I.B. acknowledges financial support from the German Research Foundation (project no. 450169704). Publisher Copyright: © 2024 The Authors. Published by American Chemical Society. | |
| dc.description.abstract | Radiation cancer therapies use different ionizing radiation qualities that damage DNA molecules in tumor cells by a yet not completely understood plethora of mechanisms and processes. While the direct action of the radiation is significant, the byproducts of the water radiolysis, mainly secondary low-energy electrons (LEEs, <20 eV) and reactive oxygen species (ROS), can also efficiently cause DNA damage, in terms of DNA strand breakage or DNA interstrand cross-linking. As a result, these types of DNA damage evolve into mutations hindering DNA replication, leading to cancer cell death. Concomitant chemo-radiotherapy explores the addition of radiosensitizing therapeutics commonly targeting DNA, such as platinum derivatives and halogenated nucleosides, to enhance the harmful effects of ionizing radiation on the DNA molecule. Further complicating the landscape of DNA damage are secondary structures such as G-quadruplexes occurring in telomeric DNA. These structures protect DNA from radiation damage, rendering them as promising targets for new and more selective cancer radiation treatments, rather than targeting linear DNA. However, despite extensive research, there is no single paradigm approach to understanding the mysterious way in which ionizing radiation causes DNA damage. This is due to the multidisciplinary nature of the field of research, which deals with multiple levels of biological organization, from the molecular building blocks of life toward cells and organisms, as well as with complex multiscale radiation-induced effects. Also, intrinsic DNA features, such as DNA topology and specific oligonucleotide sequences, strongly influence its response to damage from ionizing radiation. In this Account, we present our studies focused on the absolute quantification of photon- and low-energy electron-induced DNA damage in strategically selected target DNA sequences. Our methodology involves using DNA origami nanostructures, specifically the Rothemund triangle, as a platform to expose DNA sequences to either low-energy electrons or vacuum-ultraviolet (VUV, <15 eV) photons and subsequent atomic force microscopy (AFM) analysis. Through this approach, the effects of the DNA sequence, incorporation of halogenated radiosensitizers, DNA topology, and the radiation quality on radiation-induced DNA strand breakage have been systematically assessed and correlated with fundamental photon- and electron-driven mechanisms underlying DNA radiation damage. At lower energies, these mechanisms include dissociative electron attachment (DEA), where electrons attach to DNA molecules causing strand breaks, and dissociative photoexcitation of DNA. Additionally, further dissociative processes such as photoionization and electron impact contribute to the complex cascade of DNA damage events induced by ionizing radiation. We expect that emerging DNA origami-based approaches will lead to a paradigm shift in research fields associated with DNA damage and suggest future directions, which can foster the development of technological applications in nanomedicine, e.g., optimized cancer treatments or the molecular design of optimized radiosensitizing therapeutics. | en |
| dc.description.version | publishersversion | |
| dc.description.version | published | |
| dc.format.extent | 12 | |
| dc.format.extent | 5875258 | |
| dc.identifier.doi | 10.1021/acs.accounts.4c00121 | |
| dc.identifier.issn | 0001-4842 | |
| dc.identifier.other | PURE: 99833115 | |
| dc.identifier.other | PURE UUID: 4fb9ddc1-2d21-49f8-8276-b1a9a56b19e0 | |
| dc.identifier.other | Scopus: 85194173537 | |
| dc.identifier.other | WOS: 001230333000001 | |
| dc.identifier.other | PubMed: 38780304 | |
| dc.identifier.other | PubMedCentral: PMC11154965 | |
| dc.identifier.uri | http://hdl.handle.net/10362/172650 | |
| dc.identifier.url | https://www.scopus.com/pages/publications/85194173537 | |
| dc.language.iso | eng | |
| dc.peerreviewed | yes | |
| dc.subject | General Chemistry | |
| dc.subject | SDG 3 - Good Health and Well-being | |
| dc.title | Unraveling the Complexity of DNA Radiation Damage Using DNA Nanotechnology | en |
| dc.type | journal article | |
| degois.publication.firstPage | 1608 | |
| degois.publication.issue | 11 | |
| degois.publication.lastPage | 1619 | |
| degois.publication.title | Accounts of Chemical Research | |
| degois.publication.volume | 57 | |
| dspace.entity.type | Publication | |
| rcaap.rights | openAccess |
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