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Yeast Rad52 is a homodecamer and possesses BRCA2-like bipartite Rad51 binding modes

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Listed:
  • Jaigeeth Deveryshetty

    (Saint Louis University School of Medicine)

  • Rahul Chadda

    (Saint Louis University School of Medicine)

  • Jenna R. Mattice

    (Montana State University)

  • Simrithaa Karunakaran

    (Saint Louis University School of Medicine)

  • Michael J. Rau

    (Washington University in St. Louis School of Medicine)

  • Katherine Basore

    (Washington University in St. Louis School of Medicine)

  • Nilisha Pokhrel

    (Marquette University
    Aera Therapeutics)

  • Noah Englander

    (Saint Louis University School of Medicine)

  • James A. J. Fitzpatrick

    (Washington University in St. Louis School of Medicine)

  • Brian Bothner

    (Montana State University)

  • Edwin Antony

    (Saint Louis University School of Medicine)

Abstract

Homologous recombination (HR) is an essential double-stranded DNA break repair pathway. In HR, Rad52 facilitates the formation of Rad51 nucleoprotein filaments on RPA-coated ssDNA. Here, we decipher how Rad52 functions using single-particle cryo-electron microscopy and biophysical approaches. We report that Rad52 is a homodecameric ring and each subunit possesses an ordered N-terminal and disordered C-terminal half. An intrinsic structural asymmetry is observed where a few of the C-terminal halves interact with the ordered ring. We describe two conserved charged patches in the C-terminal half that harbor Rad51 and RPA interacting motifs. Interactions between these patches regulate ssDNA binding. Surprisingly, Rad51 interacts with Rad52 at two different bindings sites: one within the positive patch in the disordered C-terminus and the other in the ordered ring. We propose that these features drive Rad51 nucleation onto a single position on the DNA to promote formation of uniform pre-synaptic Rad51 filaments in HR.

Suggested Citation

  • Jaigeeth Deveryshetty & Rahul Chadda & Jenna R. Mattice & Simrithaa Karunakaran & Michael J. Rau & Katherine Basore & Nilisha Pokhrel & Noah Englander & James A. J. Fitzpatrick & Brian Bothner & Edwin, 2023. "Yeast Rad52 is a homodecamer and possesses BRCA2-like bipartite Rad51 binding modes," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41993-1
    DOI: 10.1038/s41467-023-41993-1
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    References listed on IDEAS

    as
    1. Roxanne Oshidari & Richard Huang & Maryam Medghalchi & Elizabeth Y. W. Tse & Nasser Ashgriz & Hyun O. Lee & Haley Wyatt & Karim Mekhail, 2020. "DNA repair by Rad52 liquid droplets," Nature Communications, Nature, vol. 11(1), pages 1-8, December.
    2. Shane McDevitt & Timur Rusanov & Tatiana Kent & Gurushankar Chandramouly & Richard T. Pomerantz, 2018. "How RNA transcripts coordinate DNA recombination and repair," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    3. Sahiti Kuppa & Jaigeeth Deveryshetty & Rahul Chadda & Jenna R. Mattice & Nilisha Pokhrel & Vikas Kaushik & Angela Patterson & Nalini Dhingra & Sushil Pangeni & Marisa K. Sadauskas & Sajad Shiekh & Ham, 2022. "Rtt105 regulates RPA function by configurationally stapling the flexible domains," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. James H. New & Tomohiko Sugiyama & Elena Zaitseva & Stephen C. Kowalczykowski, 1998. "Rad52 protein stimulates DNA strand exchange by Rad51 and replication protein A," Nature, Nature, vol. 391(6665), pages 407-410, January.
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