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A RAD51–ADP double filament structure unveils the mechanism of filament dynamics in homologous recombination

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  • Shih-Chi Luo

    (Academia Sinica)

  • Min-Chi Yeh

    (Academia Sinica
    National Taiwan University)

  • Yu-Hsiang Lien

    (Academia Sinica)

  • Hsin-Yi Yeh

    (National Taiwan University)

  • Huei-Lun Siao

    (Academia Sinica)

  • I-Ping Tu

    (Academia Sinica)

  • Peter Chi

    (Academia Sinica
    National Taiwan University)

  • Meng-Chiao Ho

    (Academia Sinica
    National Taiwan University)

Abstract

ATP-dependent RAD51 recombinases play an essential role in eukaryotic homologous recombination by catalyzing a four-step process: 1) formation of a RAD51 single-filament assembly on ssDNA in the presence of ATP, 2) complementary DNA strand-exchange, 3) ATP hydrolysis transforming the RAD51 filament into an ADP-bound disassembly-competent state, and 4) RAD51 disassembly to provide access for DNA repairing enzymes. Of these steps, filament dynamics between the ATP- and ADP-bound states, and the RAD51 disassembly mechanism, are poorly understood due to the lack of near-atomic-resolution information of the ADP-bound RAD51–DNA filament structure. We report the cryo-EM structure of ADP-bound RAD51–DNA filaments at 3.1 Å resolution, revealing a unique RAD51 double-filament that wraps around ssDNA. Structural analysis, supported by ATP-chase and time-resolved cryo-EM experiments, reveals a collapsing mechanism involving two four-protomer movements along ssDNA for mechanical transition between RAD51 single- and double-filament without RAD51 dissociation. This mechanism enables elastic change of RAD51 filament length during structural transitions between ATP- and ADP-states.

Suggested Citation

  • Shih-Chi Luo & Min-Chi Yeh & Yu-Hsiang Lien & Hsin-Yi Yeh & Huei-Lun Siao & I-Ping Tu & Peter Chi & Meng-Chiao Ho, 2023. "A RAD51–ADP double filament structure unveils the mechanism of filament dynamics in homologous recombination," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40672-5
    DOI: 10.1038/s41467-023-40672-5
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    as
    1. Shih-Chi Luo & Hsin-Yi Yeh & Wei-Hsuan Lan & Yi-Min Wu & Cheng-Han Yang & Hao-Yen Chang & Guan-Chin Su & Chia-Yi Lee & Wen-Jin Wu & Hung-Wen Li & Meng-Chiao Ho & Peter Chi & Ming-Daw Tsai, 2021. "Identification of fidelity-governing factors in human recombinases DMC1 and RAD51 from cryo-EM structures," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    2. Joost van Mameren & Mauro Modesti & Roland Kanaar & Claire Wyman & Erwin J. G. Peterman & Gijs J. L. Wuite, 2009. "Counting RAD51 proteins disassembling from nucleoprotein filaments under tension," Nature, Nature, vol. 457(7230), pages 745-748, February.
    3. Haijuan Yang & Chun Zhou & Ankita Dhar & Nikola P. Pavletich, 2020. "Mechanism of strand exchange from RecA–DNA synaptic and D-loop structures," Nature, Nature, vol. 586(7831), pages 801-806, October.
    4. Michael G. Sehorn & Stefan Sigurdsson & Wendy Bussen & Vinzenz M. Unger & Patrick Sung, 2004. "Human meiotic recombinase Dmc1 promotes ATP-dependent homologous DNA strand exchange," Nature, Nature, vol. 429(6990), pages 433-437, May.
    5. Zhucheng Chen & Haijuan Yang & Nikola P. Pavletich, 2008. "Mechanism of homologous recombination from the RecA–ssDNA/dsDNA structures," Nature, Nature, vol. 453(7194), pages 489-494, May.
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