Radiation-induced DNA damage and repair effects on 3D genome organization

Jacob T. Sanders, Trevor F. Freeman, Yang Xu, Rosela Golloshi, Mary A. Stallard, Ashtyn M. Hill, Rebeca San Martin, Adayabalam S. Balajee and Rachel Patton McCord ()
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Jacob T. Sanders: University of Tennessee
Trevor F. Freeman: University of Tennessee
Yang Xu: University of Tennessee
Rosela Golloshi: University of Tennessee
Mary A. Stallard: University of Tennessee
Ashtyn M. Hill: University of Tennessee
Rebeca San Martin: University of Tennessee
Adayabalam S. Balajee: Oak Ridge Associated Universities
Rachel Patton McCord: University of Tennessee

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-20047-w

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