HRR is a major pathway for the resolution of DNA double-strand breaks (DSBs) in the somatic
FLAG Peptide of higher eukaryotes, and is mediated by RAD51, the eukaryal orthologue of bacterial RecA. A key step in HRR involves the assembly of RAD51 onto DNA substrates at the site of DNA breakage to form an ordered, helical nucleoprotein filament, which catalyzes homologous pairing and the strand exchange reaction [1]. This RAD51 assembly is marked in cells by the formation of nuclear foci containing RAD51 in vertebrate cells of avian, rodent or human origin. Genetic studies in these organisms demonstrate that a number of ancillary
molecules are necessary for RAD51 focus formation after DNA damage. These include the breast cancer suppressor, BRCA2, as well as the RAD51 paralogues XRCC2, XRCC3 and RAD51B-D. Available evidence suggests that these ancillary molecules assist RAD51 focus formation either by working as ‘recombination mediators’, which displace proteins like replication protein A from DNA to enable RAD51 nucleation, or by directly promoting RAD51 loading [2] and [3]. An important unresolved question concerns the nature of the signaling process that triggers RAD51 assembly at sites of DNA breakage.
