RAD51-single-stranded DNA nucleoprotein filament (RAD51-ssDNA filament) (RAD51-ssDNA filament)

The RAD51–single-stranded DNA (ssDNA) nucleoprotein filament is a right-handed helical assembly that serves as the essential catalytic intermediate in homologous recombination (HR) [1, 3, 6]. It is formed when RAD51 recombinase monomers polymerize onto ssDNA, a process regulated by mediator proteins such as BRCA2 and the RAD51 paralogs, which assist in displacing replication protein A (RPA) from the DNA [1, 12, 15, 21]. Once assembled, the filament performs a homology search within double-stranded DNA and catalyzes strand invasion to form a displacement loop (D-loop), enabling high-fidelity repair of double-strand breaks [6, 12, 13, 14]. Additionally, the filament plays a critical role in protecting stalled replication forks from degradation, thereby preserving genomic integrity during S-phase [3, 12, 18]. In many human cancers, RAD51 is overexpressed, leading to hyperactive HR that confers resistance to DNA-damaging chemotherapy and ionizing radiation [2, 4, 7, 16]. Therapeutic strategies targeting this filament include small molecules that inhibit its assembly, disrupt protomer interactions, or block strand exchange, with the goal of sensitizing tumor cells to conventional treatments, particularly in the context of synthetic lethality [4, 7, 9, 11].

Other names

Presynaptic filamentRAD51-ssDNA complexRAD51-ssDNA polymerRAD51-ssDNA nucleoprotein filament

Inhibition of RAD51-ssDNA nucleoprotein filament assembly, disruption of RAD51 protomer-protomer interactions, inhibition of DNA strand exchange, and stimulation of filament formation.