PT  - JOURNAL ARTICLE
AU  - Jacob T. Sanders
AU  - Trevor F. Freeman
AU  - Yang Xu
AU  - Rosela Golloshi
AU  - Mary A. Stallard
AU  - Rebeca San Martin
AU  - Adayabalam S. Balajee
AU  - Rachel Patton McCord
TI  - Radiation-Induced DNA Damage and Repair Effects on 3D Genome Organization
AID  - 10.1101/740704
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 740704
4099  - http://biorxiv.org/content/early/2019/08/20/740704.short
4100  - http://biorxiv.org/content/early/2019/08/20/740704.full
AB  - 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. Fibroblasts, lymphoblasts, and ATM-deficient fibroblasts were irradiated with 5 Gy X-rays and Hi-C was performed after 30 minutes, 24 hours, or 5 days after irradiation. 3D genome changes after irradiation were cell type-specific, with lymphoblastoid cells generally showing more contact changes than irradiated fibroblasts. However, all tested repair-proficient cell types exhibited an increased segregation of topologically associating domains (TADs). This TAD boundary strengthening after irradiation was not observed in ATM deficient fibroblasts and may indicate the presence of a mechanism to protect 3D genome structure integrity during DNA damage repair.