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

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.

Description

Keywords

yeast, DNA, homodecamer, binding modes, Homologous recombination (HR), Rad52

Citation

Deveryshetty, J., Chadda, R., Mattice, J.R. et al. Yeast Rad52 is a homodecamer and possesses BRCA2-like bipartite Rad51 binding modes. Nat Commun 14, 6215 (2023). https://doi.org/10.1038/s41467-023-41993-1
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