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Perinuclear tethers license telomeric DSBs for a broad kinesin- and NPC-dependent DNA repair process

Author

Listed:
  • Daniel K.C. Chung

    (University of Toronto)

  • Janet N.Y. Chan

    (University of Toronto)

  • Jonathan Strecker

    (University of Toronto
    Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital)

  • Wei Zhang

    (University of Toronto
    Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital)

  • Sasha Ebrahimi-Ardebili

    (University of Toronto)

  • Thomas Lu

    (University of Toronto)

  • Karan J. Abraham

    (University of Toronto)

  • Daniel Durocher

    (University of Toronto
    Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
    Canada Research Chairs Program, University of Toronto)

  • Karim Mekhail

    (University of Toronto
    Canada Research Chairs Program, University of Toronto)

Abstract

DNA double-strand breaks (DSBs) are often targeted to nuclear pore complexes (NPCs) for repair. How targeting is achieved and the DNA repair pathways involved in this process remain unclear. Here, we show that the kinesin-14 motor protein complex (Cik1–Kar3) cooperates with chromatin remodellers to mediate interactions between subtelomeric DSBs and the Nup84 nuclear pore complex to ensure cell survival via break-induced replication (BIR), an error-prone DNA repair process. Insertion of a DNA zip code near the subtelomeric DSB site artificially targets it to NPCs hyperactivating this repair mechanism. Kinesin-14 and Nup84 mediate BIR-dependent repair at non-telomeric DSBs whereas perinuclear telomere tethers are only required for telomeric BIR. Furthermore, kinesin-14 plays a critical role in telomerase-independent telomere maintenance. Thus, we uncover roles for kinesin and NPCs in DNA repair by BIR and reveal that perinuclear telomere anchors license subtelomeric DSBs for this error-prone DNA repair mechanism.

Suggested Citation

  • Daniel K.C. Chung & Janet N.Y. Chan & Jonathan Strecker & Wei Zhang & Sasha Ebrahimi-Ardebili & Thomas Lu & Karan J. Abraham & Daniel Durocher & Karim Mekhail, 2015. "Perinuclear tethers license telomeric DSBs for a broad kinesin- and NPC-dependent DNA repair process," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8742
    DOI: 10.1038/ncomms8742
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