The presynaptic phase of homologous DNA pairing and strand exchange begins with the displacement of RPA from ssDNA, followed by the association of RAD51 with BRCA2, formation of RAD52 heptameric ring structure complexes on ssDNA, association of RAD52 with the RPA complex, association of RAD52 with ssDNA at resected ends of double-strand break and assembly of the RAD51-ssDNA nucleoprotein complex. Stable synaptic pairing between recombining DNA molecules involves the invasion of homologous duplex DNA by the processed single-stranded ends of the double-strand break, followed by displacement of the non-complimentary strand of the duplex. This results in the formation of a D-loop structure. Invasion of the heteroduplex DNA by RAD51 nucleoprotein filament involves the identification of a region of homology between these two molecules. The mechanism by which this occurs is not yet known. RAD51 catalyses the invasion of the nucleoprotein filament into homologous double-stranded DNA. Watson-Crick hydrogen bonding between the ssDNA within the nucleoprotein filament and the homologous strand of the invaded DNA duplex result in the displacement of the non-pairing strand (strand displacement) and formation of the D-loop structure (Sung et al., 2003).
The RAD51 nucleoprotein filament has independent binding sites for the ssDNA strand upon which it assembles and the recombining homologous duplex DNA. The repair proteins RPA, RAD52, and RAD54 appear to promote RAD51 mediated invasion and homologous DNA pairing reaction (McIlwraith et al, 2000 and Sigurdsson et al., 2002). The conformation of the RAD52-ssDNA complex is thought to place the ssDNA on an exposed surface of the protein, in a configuration that may promote the DNA-DNA annealing of complementary DNA strands. RAD54 may function in the transient separation of the duplex DNA strands via its ATP hydrolysis-mediated DNA supercoiling function (Sigurdsson et al., 2002). Branch migration or strand exchange occurs as the complimentary duplex DNA strand is progressively taken up into the nucleoprotein filament to base pair with the invading single-strand sequence (Sung et al., 2003).