Cryo-electron microscopic visualization of RAD51 filament assembly and end-capping by XRCC3-RAD51C-RAD51D-XRCC2
Summary
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
Content
# Cryo-electron microscopic visualization of RAD51 filament assembly and end-capping by XRCC3-RAD51C-RAD51D-XRCC2
*Published: 2026 Feb 26*
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, the XRCC3 complex reveals insights into RAD51 filament
formation and capping during DNA repair and replication fork stabilization.
DOI: 10.1126/science.aea1546