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TitleCryo-electron microscopy visualization of RAD51 filament assembly and end-capping by XRCC3-RAD51C-RAD51D-XRCC2.
Journal, issue, pagesScience, Page eaea1546, Year 2025
Publish dateNov 6, 2025
AuthorsLuke A Greenhough / Lorenzo Galanti / Chih-Chao Liang / Simon J Boulton / Stephen C West /
PubMed AbstractHomologous recombination repairs DNA double strand breaks and protects stalled replication forks, but how the five RAD51 paralogs contribute to these processes remains unclear. Mutations in the RAD51 ...Homologous recombination repairs DNA double strand breaks and protects stalled replication forks, but how the five RAD51 paralogs contribute to these processes remains unclear. Mutations in the RAD51 paralogs are linked to heritable breast and ovarian cancers and the cancer-prone disease Fanconi anemia. In this work, we show that the RAD51 paralogs assemble into two distinct heterotetrameric complexes, RAD51B-RAD51C-RAD51D-XRCC2 (RAD51B complex) and XRCC3-RAD51C-RAD51D-XRCC2 (XRCC3 complex). The RAD51B complex promotes dynamic adenosine triphosphate hydrolysis-dependent assembly of RAD51 filaments, whereas the XRCC3 complex stably caps the 5'-termini of RAD51 filaments to promote homologous pairing, as visualized by cryo-electron microscopy. Highly conserved across evolution, these complexes reveal insights into RAD51 filament formation and capping during DNA repair and replication fork stabilization.
External linksScience / PubMed:41196948 / PubMed Central
MethodsEM (single particle)
Resolution2.6 - 3.0 Å
Structure data

55290

9svx

EMDB-55290, PDB-9svx:
XRCC3-RAD51C-RAD51D-XRCC2 (XRCC3 complex) capping a RAD51 filament on single stranded DNA
Method: EM (single particle) / Resolution: 2.7 Å

55291

9svy

EMDB-55291, PDB-9svy:
XRCC3-RAD51C-RAD51D-XRCC2 (XRCC3 complex) capping a RAD51 filament on partially duplex DNA
Method: EM (single particle) / Resolution: 2.6 Å

55292

9sw0

EMDB-55292, PDB-9sw0:
XRCC3-RAD51C-RAD51D-XRCC2 (XRCC3 complex) capping a RAD51 filament on a D-loop intermediate
Method: EM (single particle) / Resolution: 3.0 Å

Chemicals

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-CA:
Unknown entry

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsDNA BINDING PROTEIN / complex / tumor suppresor

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