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The essential elements for the noncovalent association of two DNA ends during NHEJ synapsis

Author

Listed:
  • Bailin Zhao

    (USC Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine)

  • Go Watanabe

    (USC Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine)

  • Michael J. Morten

    (New York University School of Medicine)

  • Dylan A. Reid

    (New York University School of Medicine)

  • Eli Rothenberg

    (New York University School of Medicine)

  • Michael R. Lieber

    (USC Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine)

Abstract

One of the most central questions about the repair of a double-strand DNA break (DSB) concerns how the two free DNA ends are brought together — a step called synapsis. Using single-molecule FRET (smFRET), we show here that both Ku plus XRCC4:DNA ligase IV are necessary and sufficient to achieve a flexible synapsis of blunt DNA ends, whereas either alone is not. Addition of XLF causes a transition to a close synaptic state, and maximum efficiency of close synapsis is achieved within 20 min. The promotion of close synapsis by XLF indicates a role that is independent of a filament structure, with action focused at the very ends of each duplex. DNA-PKcs is not required for the formation of either the flexible or close synaptic states. This model explains in biochemical terms the evolutionarily central synaptic role of Ku, X4L4, and XLF in NHEJ for all eukaryotes.

Suggested Citation

  • Bailin Zhao & Go Watanabe & Michael J. Morten & Dylan A. Reid & Eli Rothenberg & Michael R. Lieber, 2019. "The essential elements for the noncovalent association of two DNA ends during NHEJ synapsis," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11507-z
    DOI: 10.1038/s41467-019-11507-z
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    Cited by:

    1. Jenny Kaur Singh & Rebecca Smith & Magdalena B. Rother & Anton J. L. Groot & Wouter W. Wiegant & Kees Vreeken & Ostiane D’Augustin & Robbert Q. Kim & Haibin Qian & Przemek M. Krawczyk & Román González, 2021. "Zinc finger protein ZNF384 is an adaptor of Ku to DNA during classical non-homologous end-joining," Nature Communications, Nature, vol. 12(1), pages 1-21, December.
    2. 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.
    3. Metztli Cisneros-Aguirre & Felicia Wednesday Lopezcolorado & Linda Jillianne Tsai & Ragini Bhargava & Jeremy M. Stark, 2022. "The importance of DNAPKcs for blunt DNA end joining is magnified when XLF is weakened," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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