Logo image
The human RAD52 complex undergoes phase separation and facilitates bundling and end-to-end tethering of RAD51 presynaptic filaments
Journal article   Open access   Peer reviewed

The human RAD52 complex undergoes phase separation and facilitates bundling and end-to-end tethering of RAD51 presynaptic filaments

Ibraheem Alshareedah, Sushil Pangeni, Paul A Dewan Jr, Masayoshi Honda, Ting-Wei Liao, Maria Spies and Taekjip Ha
Nucleic acids research, Vol.54(3), gkag043
01/22/2026
DOI: 10.1093/nar/gkag043
PMID: 41603734
url
https://doi.org/10.1093/nar/gkag043View
Published (Version of record) Open Access

Abstract

Human RAD52 is a prime target for synthetic lethality approaches to treat cancers with deficiency in homologous recombination. Among multiple cellular roles, RAD52's functions in homologous recombination repair and stalled replication fork protection appear to substitute for those of the tumor suppressor protein BRCA2. However, the mechanistic details of how RAD52 substitutes for BRCA2 functions are only beginning to emerge. RAD52 forms an oligomeric ring enveloped by ∼200-residue-long disordered regions, forming a highly multivalent and branched protein complex that promotes supramolecular assembly. Here, we demonstrate that RAD52 undergoes homotypic phase separation, forming condensates that recruit key homologous recombination factors, including single-stranded DNA (ssDNA), replication protein A (RPA), and the RAD51 recombinase. Furthermore, we show that RAD52 phase separation is regulated by its interaction partners such as ssDNA and RPA. Through fluorescence microscopy, we observe that RAD52 promotes the formation of RAD51-ssDNA fibrillar structures. To resolve the fine architecture of these fibrils, we employed single-molecule super-resolution imaging via DNA-PAINT and atomic force microscopy, revealing that RAD51 fibrils comprise bundles of individual RAD51 nucleoprotein filaments. Additionally, we show that RAD52 induces end-to-end tethering of RAD51 nucleoprotein filaments. Collectively, these findings highlight distinctive macromolecular organizational features of RAD52 that may underpin its diverse cellular functions.
BRCA2 Protein - genetics DNA, Single-Stranded - genetics DNA, Single-Stranded - metabolism Homologous Recombination Humans Phase Separation Protein Binding Rad51 Recombinase - chemistry Rad51 Recombinase - genetics Rad51 Recombinase - metabolism Rad52 DNA Repair and Recombination Protein - chemistry Rad52 DNA Repair and Recombination Protein - genetics Rad52 DNA Repair and Recombination Protein - metabolism Replication Protein A - genetics Replication Protein A - metabolism

Details

Metrics

1 Record Views
Logo image