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What Does the History of Research on the Repair of DNA Double-Strand Breaks Tell Us?—A Comprehensive Review of Human Radiosensitivity

Our understanding of the molecular and cellular response to ionizing radiation (IR) has progressed considerably. This is notably the case for the repair and signaling of DNA double-strand breaks (DSB) that, if unrepaired, can result in cell lethality, or if misrepaired, can cause cancer. However, th...

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Autores principales: Berthel, Elise, Ferlazzo, Mélanie L., Devic, Clément, Bourguignon, Michel, Foray, Nicolas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862552/
https://www.ncbi.nlm.nih.gov/pubmed/31717816
http://dx.doi.org/10.3390/ijms20215339
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author Berthel, Elise
Ferlazzo, Mélanie L.
Devic, Clément
Bourguignon, Michel
Foray, Nicolas
author_facet Berthel, Elise
Ferlazzo, Mélanie L.
Devic, Clément
Bourguignon, Michel
Foray, Nicolas
author_sort Berthel, Elise
collection PubMed
description Our understanding of the molecular and cellular response to ionizing radiation (IR) has progressed considerably. This is notably the case for the repair and signaling of DNA double-strand breaks (DSB) that, if unrepaired, can result in cell lethality, or if misrepaired, can cause cancer. However, through the different protocols, techniques, and cellular models used during the last four decades, the DSB repair kinetics and the relationship between cellular radiosensitivity and unrepaired DSB has varied drastically, moving from all-or-none phenomena to very complex mechanistic models. To date, personalized medicine has required a reliable evaluation of the IR-induced risks that have become a medical, scientific, and societal issue. However, the molecular bases of the individual response to IR are still unclear: there is a gap between the moderate radiosensitivity frequently observed in clinic but poorly investigated in the publications and the hyper-radiosensitivity of rare but well-characterized genetic diseases frequently cited in the mechanistic models. This paper makes a comprehensive review of semantic issues, correlations between cellular radiosensitivity and unrepaired DSB, shapes of DSB repair curves, and DSB repair biomarkers in order to propose a new vision of the individual response to IR that would be more coherent with clinical reality.
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spelling pubmed-68625522019-12-05 What Does the History of Research on the Repair of DNA Double-Strand Breaks Tell Us?—A Comprehensive Review of Human Radiosensitivity Berthel, Elise Ferlazzo, Mélanie L. Devic, Clément Bourguignon, Michel Foray, Nicolas Int J Mol Sci Review Our understanding of the molecular and cellular response to ionizing radiation (IR) has progressed considerably. This is notably the case for the repair and signaling of DNA double-strand breaks (DSB) that, if unrepaired, can result in cell lethality, or if misrepaired, can cause cancer. However, through the different protocols, techniques, and cellular models used during the last four decades, the DSB repair kinetics and the relationship between cellular radiosensitivity and unrepaired DSB has varied drastically, moving from all-or-none phenomena to very complex mechanistic models. To date, personalized medicine has required a reliable evaluation of the IR-induced risks that have become a medical, scientific, and societal issue. However, the molecular bases of the individual response to IR are still unclear: there is a gap between the moderate radiosensitivity frequently observed in clinic but poorly investigated in the publications and the hyper-radiosensitivity of rare but well-characterized genetic diseases frequently cited in the mechanistic models. This paper makes a comprehensive review of semantic issues, correlations between cellular radiosensitivity and unrepaired DSB, shapes of DSB repair curves, and DSB repair biomarkers in order to propose a new vision of the individual response to IR that would be more coherent with clinical reality. MDPI 2019-10-26 /pmc/articles/PMC6862552/ /pubmed/31717816 http://dx.doi.org/10.3390/ijms20215339 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Berthel, Elise
Ferlazzo, Mélanie L.
Devic, Clément
Bourguignon, Michel
Foray, Nicolas
What Does the History of Research on the Repair of DNA Double-Strand Breaks Tell Us?—A Comprehensive Review of Human Radiosensitivity
title What Does the History of Research on the Repair of DNA Double-Strand Breaks Tell Us?—A Comprehensive Review of Human Radiosensitivity
title_full What Does the History of Research on the Repair of DNA Double-Strand Breaks Tell Us?—A Comprehensive Review of Human Radiosensitivity
title_fullStr What Does the History of Research on the Repair of DNA Double-Strand Breaks Tell Us?—A Comprehensive Review of Human Radiosensitivity
title_full_unstemmed What Does the History of Research on the Repair of DNA Double-Strand Breaks Tell Us?—A Comprehensive Review of Human Radiosensitivity
title_short What Does the History of Research on the Repair of DNA Double-Strand Breaks Tell Us?—A Comprehensive Review of Human Radiosensitivity
title_sort what does the history of research on the repair of dna double-strand breaks tell us?—a comprehensive review of human radiosensitivity
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862552/
https://www.ncbi.nlm.nih.gov/pubmed/31717816
http://dx.doi.org/10.3390/ijms20215339
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