Endogenous DNA Double-Strand Breaks during DNA Transactions: Emerging Insights and Methods for Genome-Wide Profiling
by
Britta A. M. Bouwman *
and Nicola Crosetto *
Britta A. M. Bouwman * and Nicola Crosetto *
Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17165 Stockholm, Sweden
*
Authors to whom correspondence should be addressed.
Genes 2018, 9(12), 632; https://doi.org/10.3390/genes9120632
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)
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.
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Keywords:
DNA double-strand breaks; replication; transcription; chromatin looping; topoisomerases; cancer; rearrangements; genome-wide methods; 3D genome structure
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MDPI and ACS Style
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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