BCDX2–CX3 and DX2–CX3 complexes assemble and stabilize RAD51 filaments

Article Published: 02 March 2026 BCDX2–CX3 and DX2–CX3 complexes assemble and stabilize RAD51 filaments Christopher W. Koo 1 , Jiaqi Xiao ( 肖嘉祺 ) 1 , Sebastien Coassolo ORCID: orcid.org/0000-0003-3669-8650 2 , Jie Liu ORCID: orcid.org/0000-0001-5817-9144 3 , Christine Yu 1 , Caleigh Azumaya ORCID: orcid.org/0000-0002-3484-9921 1 , Steven K. Gore ORCID: orcid.org/0009-0003-4901-7671 3 , Tommy K. Cheung 4 , Bobby Brillantes 1 , Chris M. Rose 4 , Wolf-Dietrich Heyer ORCID: orcid.org/0000-0002-7774-1953 3 , Claudio Ciferri ORCID: orcid.org/0000-0002-0804-2411 1 & … Stanislau Yatskevich ORCID: orcid.org/0000-0003-2999-6561 1 Show authors Nature ( 2026 ) Cite this article We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply. Subjects Cryoelectron microscopy DNA Homologous recombination Abstract The repair of DNA double-strand breaks by homologous recombination is essential for genomic integrity, and its dysregulation is a hallmark of cancer 1 . Central to HR is the RAD51 recombinase, whose assembly into a nucleoprotein filament is governed by five RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, XRCC3) 2 . Mutations in any of these proteins predispose individuals to multiple cancers or genetic disorders 3-6 . These paralogs are thought to form two functionally separate complexes, BCDX2 (RAD51B-C-D-XRCC2) and CX3 (RAD51C-XRCC3), that act independently at different stages of HR 7-11 . Here, we demonstrate that all five paralogs can assemble into a single, ATP-dependent BCDX2-CX3-RAD51 supercomplex. The architecture of this assembly bound to single-stranded DNA reveals a contiguous filament where the CX3 module stacks atop BCDX2, creating a protofilament template for RAD51 filament formation. We further identify a novel, RAD51B-independent DX2-CX3 complex (RAD51D-XRCC2-R...