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Mechanisms and Consequences of Double‐Strand DNA Break Formation in Chromatin
Open accessAbstract
All organisms suffer double‐strand breaks (DSBs) in their DNA as a result of exposure to ionizing radiation. DSBs can also form when replication forks encounter DNA lesions or repair intermediates. The processing and repair of DSBs can lead to mutations, loss of heterozygosity, and chromosome rearrangements that result in cell death or cancer. The most common pathway used to repair DSBs in metazoans (non‐homologous DNA end joining) is more commonly mutagenic than the alternative pathway (homologous recombination mediated repair). Thus, factors that influence the choice of pathways used DSB repair can affect an individual's mutation burden and risk of cancer. This review describes radiological, chemical, and biological mechanisms that generate DSBs, and discusses the impact of such variables as DSB etiology, cell type, cell cycle, and chromatin structure on the yield, distribution, and processing of DSBs. The final section focuses on nucleosome‐specific mechanisms that influence DSB production, and the possible relationship between higher order chromosome coiling and chromosome shattering (chromothripsis). J. Cell. Physiol. 230: 3–14, 2016. © 2015 Wiley Periodicals, Inc.
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“SSBs may form DSBs through their collision with the transcriptional machinery and replication forks, or through their close proximity to another SSB.”
From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Cannan & Pederson, 2016
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“DSBs are also directly generated by transcription (Cannan & Pederson, 2016), whereby topoisomerase II (TOP2) induces transient DSBs to relieve torsional stress and facilitate gene expression.”
From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Cannan & Pederson, 2016
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Metadata
- Authors
- Cannan, W. J., & Pederson, D. S.
- Affiliations
- University of Vermont (US)
- Corresponding author
- Pederson, David S.
- ORCID
- Cannan, Wendy J.
- Venue
- Journal of Cellular Physiology
- Publisher
- Wiley
- Published
- 2015-09-28
- Volume
- 231
- Issue
- 1
- Pages
- 3-14
- ISSN
- 0021-9541 (ISSN-L)
- 1097-4652
- PMC
- PMC4994891
- OpenAlex
- W1783508367
- Cited by
- 499
- References
- 153
- Citations by year
- 2026: 46 · 2025: 70 · 2024: 92 · 2023: 60 · 2022: 51 · 2021: 63 · 2020: 57 · 2019: 29 · 2018: 14 · 2017: 7 · 2016: 8 · 2015: 1
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Cellular Physiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NCI (P01-CA098993)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- DNA double-strand breaks, chromatin, ionizing radiation, DNA damage mechanisms, DNA repair pathways, non-homologous end joining, homologous recombination, mutational burden, loss of heterozygosity, chromosomal rearrangements, nucleosome, chromatin structure, cell cycle, replication fork stalling, chromothripsis, chromosome coiling
- MeSH terms
- Animals, Cell Cycle, Chromatin, DNA Repair, Humans, Radiation, Ionizing, DNA Breaks, Double-Stranded, DNA End-Joining Repair
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