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Genes 2018, 9(12), 632; https://doi.org/10.3390/genes9120632

Endogenous DNA Double-Strand Breaks during DNA Transactions: Emerging Insights and Methods for Genome-Wide Profiling

Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17165 Stockholm, Sweden
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Received: 9 November 2018 / Revised: 11 December 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
(This article belongs to the Special Issue Chromosome Replication and Genome Integrity)
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Abstract

DNA double-strand breaks (DSBs) jeopardize genome integrity and can—when repaired unfaithfully—give rise to structural rearrangements associated with cancer. Exogenous agents such as ionizing radiation or chemotherapy can invoke DSBs, but a vast amount of breakage arises during vital endogenous DNA transactions, such as replication and transcription. Additionally, chromatin looping involved in 3D genome organization and gene regulation is increasingly recognized as a possible contributor to DSB events. In this review, we first discuss insights into the mechanisms of endogenous DSB formation, showcasing the trade-off between essential DNA transactions and the intrinsic challenges that these processes impose on genomic integrity. In the second part, we highlight emerging methods for genome-wide profiling of DSBs, and discuss future directions of research that will help advance our understanding of genome-wide DSB formation and repair. View Full-Text
Keywords: DNA double-strand breaks; replication; transcription; chromatin looping; topoisomerases; cancer; rearrangements; genome-wide methods; 3D genome structure DNA double-strand breaks; replication; transcription; chromatin looping; topoisomerases; cancer; rearrangements; genome-wide methods; 3D genome structure
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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 (CC BY 4.0).
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Bouwman, B.A.M.; Crosetto, N. Endogenous DNA Double-Strand Breaks during DNA Transactions: Emerging Insights and Methods for Genome-Wide Profiling. Genes 2018, 9, 632.

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