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Physiological Roles of DNA Double-Strand Breaks

Genomic integrity is constantly threatened by sources of DNA damage, internal and external alike. Among the most cytotoxic lesions is the DNA double-strand break (DSB) which arises from the cleavage of both strands of the double helix. Cells boast a considerable set of defences to both prevent and r...

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Detalles Bibliográficos
Autores principales: Khan, Farhaan A., Ali, Syed O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664317/
https://www.ncbi.nlm.nih.gov/pubmed/29181194
http://dx.doi.org/10.1155/2017/6439169
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author Khan, Farhaan A.
Ali, Syed O.
author_facet Khan, Farhaan A.
Ali, Syed O.
author_sort Khan, Farhaan A.
collection PubMed
description Genomic integrity is constantly threatened by sources of DNA damage, internal and external alike. Among the most cytotoxic lesions is the DNA double-strand break (DSB) which arises from the cleavage of both strands of the double helix. Cells boast a considerable set of defences to both prevent and repair these breaks and drugs which derail these processes represent an important category of anticancer therapeutics. And yet, bizarrely, cells deploy this very machinery for the intentional and calculated disruption of genomic integrity, harnessing potentially destructive DSBs in delicate genetic transactions. Under tight spatiotemporal regulation, DSBs serve as a tool for genetic modification, widely used across cellular biology to generate diverse functionalities, ranging from the fundamental upkeep of DNA replication, transcription, and the chromatin landscape to the diversification of immunity and the germline. Growing evidence points to a role of aberrant DSB physiology in human disease and an understanding of these processes may both inform the design of new therapeutic strategies and reduce off-target effects of existing drugs. Here, we review the wide-ranging roles of physiological DSBs and the emerging network of their multilateral regulation to consider how the cell is able to harness DNA breaks as a critical biochemical tool.
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spelling pubmed-56643172017-11-27 Physiological Roles of DNA Double-Strand Breaks Khan, Farhaan A. Ali, Syed O. J Nucleic Acids Review Article Genomic integrity is constantly threatened by sources of DNA damage, internal and external alike. Among the most cytotoxic lesions is the DNA double-strand break (DSB) which arises from the cleavage of both strands of the double helix. Cells boast a considerable set of defences to both prevent and repair these breaks and drugs which derail these processes represent an important category of anticancer therapeutics. And yet, bizarrely, cells deploy this very machinery for the intentional and calculated disruption of genomic integrity, harnessing potentially destructive DSBs in delicate genetic transactions. Under tight spatiotemporal regulation, DSBs serve as a tool for genetic modification, widely used across cellular biology to generate diverse functionalities, ranging from the fundamental upkeep of DNA replication, transcription, and the chromatin landscape to the diversification of immunity and the germline. Growing evidence points to a role of aberrant DSB physiology in human disease and an understanding of these processes may both inform the design of new therapeutic strategies and reduce off-target effects of existing drugs. Here, we review the wide-ranging roles of physiological DSBs and the emerging network of their multilateral regulation to consider how the cell is able to harness DNA breaks as a critical biochemical tool. Hindawi 2017 2017-10-18 /pmc/articles/PMC5664317/ /pubmed/29181194 http://dx.doi.org/10.1155/2017/6439169 Text en Copyright © 2017 Farhaan A. Khan and Syed O. Ali. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Khan, Farhaan A.
Ali, Syed O.
Physiological Roles of DNA Double-Strand Breaks
title Physiological Roles of DNA Double-Strand Breaks
title_full Physiological Roles of DNA Double-Strand Breaks
title_fullStr Physiological Roles of DNA Double-Strand Breaks
title_full_unstemmed Physiological Roles of DNA Double-Strand Breaks
title_short Physiological Roles of DNA Double-Strand Breaks
title_sort physiological roles of dna double-strand breaks
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664317/
https://www.ncbi.nlm.nih.gov/pubmed/29181194
http://dx.doi.org/10.1155/2017/6439169
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