Radiation-induced DNA damage and repair effects on 3D genome organization
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Abstract
The three-dimensional structure of chromosomes plays an important role in gene expression regulation and also influences the repair of radiation-induced DNA damage. Genomic aberrations that disrupt chromosome spatial domains can lead to diseases including cancer, but how the 3D genome structure responds to DNA damage is poorly understood. Here, we investigate the impact of DNA damage response and repair on 3D genome folding using Hi-C experiments on wild type cells and ataxia telangiectasia mutated (ATM) patient cells. We irradiate fibroblasts, lymphoblasts, and ATM-deficient fibroblasts with 5 Gy X-rays and perform Hi-C at 30 minutes, 24 hours, or 5 days after irradiation. We observe that 3D genome changes after irradiation are cell type-specific, with lymphoblastoid cells generally showing more contact changes than irradiated fibroblasts. However, all tested repair-proficient cell types exhibit an increased segregation of topologically associating domains (TADs). This TAD boundary strengthening after irradiation is not observed in ATM deficient fibroblasts and may indicate the presence of a mechanism to protect 3D genome structure integrity during DNA damage repair.
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DSBs have the potential to directly affect the 3D genome organization.
“DSBs have the potential to directly affect the 3D genome organization”
From Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration (2023) · cites this paper as [54]
X-ray radiation-induced DSBs increased the segregation of TAD fibroblasts.
“Surprisingly, X-ray radiation-induced DSBs increased the segregation of TAD fibroblasts54.”
From Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration (2023) · cites this paper as [54]
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References 69 · Cited by 134
- Authors
- Sanders, J. T., Freeman, T. F., Xu, Y., Golloshi, R., Stallard, M. A., Hill, A. M., San Martin, R., Balajee, A. S., & McCord, R. P.
- Affiliations
- University of Tennessee at Knoxville (US)
- Oak Ridge National Laboratory (US)
- Oak Ridge Associated Universities (US)
- Corresponding author
- McCord, Rachel Patton
- ORCID
- Venue
- Nature Communications
- Published
- 2020-12-02
- Volume
- 11
- Issue
- 1
- Pages
- 6178-6178
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7710719
- OpenAlex
- W3106938813
- Cited by
- 134
- References
- 69
- Citations by year
- 2026: 14 · 2025: 22 · 2024: 13 · 2023: 25 · 2022: 21 · 2021: 30 · 2020: 9
- FWCI
- 6.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (R35GM133557)
- Oak Ridge Associated Universities (ODRD)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- 3D genome organization, radiation-induced DNA damage, DNA repair, topologically associating domains, ATM, ataxia telangiectasia, chromatin folding, X-ray irradiation, cell type-specific responses, lymphoblastoid cell lines, fibroblasts
- MeSH terms
- Ataxia Telangiectasia, Cell Cycle, Cell Line, DNA, DNA Damage, DNA Repair, Fibroblasts, Histones, Humans, Lymphocytes, Organ Specificity, X-Rays, Gene Expression, Genome, Human, High-Throughput Nucleotide Sequencing, Ataxia Telangiectasia Mutated Proteins
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