IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-40672-5.html
   My bibliography  Save this article

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

Author

Listed:
  • 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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-40672-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-40672-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. 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.
    3. 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.
    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. 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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Michael A. Longo & Sunetra Roy & Yue Chen & Karl-Heinz Tomaszowski & Andrew S. Arvai & Jordan T. Pepper & Rebecca A. Boisvert & Selvi Kunnimalaiyaan & Caezanne Keshvani & David Schild & Albino Bacolla, 2023. "RAD51C-XRCC3 structure and cancer patient mutations define DNA replication roles," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Qi Jia & Ye Xiang, 2023. "Cryo-EM structure of a bacteriophage M13 mini variant," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. James M. Dunce & Owen R. Davies, 2024. "BRCA2 stabilises RAD51 and DMC1 nucleoprotein filaments through a conserved interaction mode," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    4. Jiaqi Yan & Rajendra Bhadane & Meixin Ran & Xiaodong Ma & Yuanqiang Li & Dongdong Zheng & Outi M. H. Salo-Ahen & Hongbo Zhang, 2024. "Development of Aptamer-DNAzyme based metal-nucleic acid frameworks for gastric cancer therapy," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    5. Kamal el Battioui & Sohini Chakraborty & András Wacha & Dániel Molnár & Mayra Quemé-Peña & Imola Cs. Szigyártó & Csenge Lilla Szabó & Andrea Bodor & Kata Horváti & Gergő Gyulai & Szilvia Bősze & Judit, 2024. "In situ captured antibacterial action of membrane-incising peptide lamellae," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40672-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.