Genome-wide detection of DNA double-strand breaks

Author(s)

Abstract

DNA double-strand breaks (DSBs) pose a major threat to genome stability, if not promptly and properly repaired. Understanding where, along the genome, DSBs arise and how they are repaired in genomic context is therefore essential to understand the biology and functional consequences of these molecular lesions. Moreover, programmable DSBs that originate from the engineered action of genome editing nucleases-such as zinc fingers, TALENs, and CRISPR nucleases-play a pivotal role both as desired mediators of the action of these enzymes as well as unwanted byproducts that threaten genome stability, when they occur away from their intended target. In the past sixteen years, a growing repertoire of methods leveraging massively parallel sequencing has emerged to map the genomic location of endogenous, physically or chemically induced, and programmed DSBs, often achieving single- nucleotide positional accuracy. In this Primer, we provide a comprehensive catalogue of these methods, highlighting their design principles together with their major strengths and limitations, describing the key biological findings enabled by these technologies, and discussing the companion toolkit needed for the analysis of the data generated by these variegated methods and their associated challenges. Lastly, we outline open questions and chart future development trajectories for this technology-driven field

Keywords

Genomics and Bioinformatics

Citation

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