Homologous DNA Pairing and Strand Exchange

The presynaptic phase of homologous DNA pairing and strand exchange begins with the displacement of RPA from 3'-ssDNA overhangs created by extensive resection of DNA double-strand break (DSB) ends. RPA is displaced by the joint action of RAD51 and BRCA2. BRCA2 nucleates RAD51 on 3'-ssDNA overhangs, leading to formation of invasive RAD51 nucleofilaments which are stabilized by the BCDX2 complex (RAD51B:RAD51C:RAD51D:XRCC2). Stable synaptic pairing between recombining DNA molecules involves the invasion of the homologous sister chromatid duplex DNA by the RAD51 nucleofilament and base-pairing between the invading ssDNA and the complementary sister chromatid DNA strand, while the non-complementary strand of the sister chromatid DNA duplex is displaced. This results in the formation of a D-loop structure. PALB2 and RAD51AP1 synergistically stimulate RAD51 recombinase activity and D-loop formation. PALB2 simultaneously interacts with RAD51, BRCA2 and RAD51AP1. PALB2 also interacts with BRCA1, and this interaction fine-tunes the localization of BRCA2 and RAD51 at DNA DSBs. The CX3 complex, composed of RAD51C and XRCC3, binds D-loop structures through interaction with PALB2 and may be involved in the resolution of Holliday junctions.

Summary from Reactome (R-HSA-5693579), read 2026-09-23.