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Journal of Nucleic Acids
Volume 2017, Article ID 6439169, 20 pages
Review Article

Physiological Roles of DNA Double-Strand Breaks

School of Clinical Medicine, Addenbrooke’s Hospital, University of Cambridge, Hills Road, Cambridge CB2 0SP, UK

Correspondence should be addressed to Syed O. Ali;

Received 8 July 2017; Accepted 24 September 2017; Published 18 October 2017

Academic Editor: Shigenori Iwai

Copyright © 2017 Farhaan A. Khan and Syed O. Ali. 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.


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.