8g3g

Publication Abstract from PubMed

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.

Yeast Rad52 is a homodecamer and possesses BRCA2-like bipartite Rad51 binding modes.,Deveryshetty J, Chadda R, Mattice JR, Karunakaran S, Rau MJ, Basore K, Pokhrel N, Englander N, Fitzpatrick JAJ, Bothner B, Antony E Nat Commun. 2023 Oct 5;14(1):6215. doi: 10.1038/s41467-023-41993-1. PMID:37798272^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.