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DNA double-strand breaks induce H2Ax phosphorylation domains in a contact-dependent manner

Author

Listed:
  • Patrick L. Collins

    (The Ohio State University)

  • Caitlin Purman

    (Washington University School of Medicine)

  • Sofia I. Porter

    (The Ohio State University)

  • Vincent Nganga

    (The Ohio State University)

  • Ankita Saini

    (The Ohio State University)

  • Katharina E. Hayer

    (Children’s Hospital of Philadelphia)

  • Greer L. Gurewitz

    (Washington University School of Medicine)

  • Barry P. Sleckman

    (University of Alabama at Birmingham)

  • Jeffrey J. Bednarski

    (Washington University School of Medicine)

  • Craig H. Bassing

    (Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania)

  • Eugene M. Oltz

    (The Ohio State University)

Abstract

Efficient repair of DNA double-strand breaks (DSBs) requires a coordinated DNA Damage Response (DDR), which includes phosphorylation of histone H2Ax, forming γH2Ax. This histone modification spreads beyond the DSB into neighboring chromatin, generating a DDR platform that protects against end disassociation and degradation, minimizing chromosomal rearrangements. However, mechanisms that determine the breadth and intensity of γH2Ax domains remain unclear. Here, we show that chromosomal contacts of a DSB site are the primary determinants for γH2Ax landscapes. DSBs that disrupt a topological border permit extension of γH2Ax domains into both adjacent compartments. In contrast, DSBs near a border produce highly asymmetric DDR platforms, with γH2Ax nearly absent from one broken end. Collectively, our findings lend insights into a basic DNA repair mechanism and how the precise location of a DSB may influence genome integrity.

Suggested Citation

  • Patrick L. Collins & Caitlin Purman & Sofia I. Porter & Vincent Nganga & Ankita Saini & Katharina E. Hayer & Greer L. Gurewitz & Barry P. Sleckman & Jeffrey J. Bednarski & Craig H. Bassing & Eugene M., 2020. "DNA double-strand breaks induce H2Ax phosphorylation domains in a contact-dependent manner," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16926-x
    DOI: 10.1038/s41467-020-16926-x
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    Cited by:

    1. Aris A. Polyzos & Ana Cheong & Jung Hyun Yoo & Lana Blagec & Sneh M. Toprani & Zachary D. Nagel & Cynthia T. McMurray, 2024. "Base excision repair and double strand break repair cooperate to modulate the formation of unrepaired double strand breaks in mouse brain," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Juan A. Perez-Bermejo & Oghene Efagene & William M. Matern & Jeffrey K. Holden & Shaheen Kabir & Glen M. Chew & Gaia Andreoletti & Eniola Catton & Craig L. Ennis & Angelica Garcia & Trevor L. Gerstenb, 2024. "Functional screening in human HSPCs identifies optimized protein-based enhancers of Homology Directed Repair," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Jin H. Yang & Hugo B. Brandão & Anders S. Hansen, 2023. "DNA double-strand break end synapsis by DNA loop extrusion," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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