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

Author

Listed:
  • 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
    University of Tennessee)

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.

Suggested Citation

  • Jacob T. Sanders & Trevor F. Freeman & Yang Xu & Rosela Golloshi & Mary A. Stallard & Ashtyn M. Hill & Rebeca San Martin & Adayabalam S. Balajee & Rachel Patton McCord, 2020. "Radiation-induced DNA damage and repair effects on 3D genome organization," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-20047-w
    DOI: 10.1038/s41467-020-20047-w
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    Cited by:

    1. Lucía Álvarez-González & Frances Burden & Dadakhalandar Doddamani & Roberto Malinverni & Emma Leach & Cristina Marín-García & Laia Marín-Gual & Albert Gubern & Covadonga Vara & Andreu Paytuví-Gallart , 2022. "3D chromatin remodelling in the germ line modulates genome evolutionary plasticity," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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