DNA repair protein RAD51–single-stranded DNA filament (RAD51-ssDNA filament)

The RAD51–single-stranded DNA (ssDNA) filament is a specialized nucleoprotein complex that serves as the central catalytic intermediate in homologous recombination (HR), a high-fidelity DNA double-strand break repair pathway [PMID: 29074303]. Formed when DNA repair protein RAD51 monomers polymerize onto 3'-overhangs of resected DNA, this right-handed helical structure facilitates the search for a homologous DNA template and catalyzes strand invasion [PMID: 18541574]. Beyond repair, these filaments play a vital role in stabilizing stalled replication forks, preventing their nucleolytic degradation and ensuring genome integrity during S-phase [PMID: 28445450]. In the context of oncology, RAD51 is frequently overexpressed in various malignancies, where it promotes resistance to DNA-damaging agents like cisplatin and ionizing radiation [PMID: 25616105]. Therapeutic strategies targeting the RAD51-ssDNA filament involve small molecules that either prevent RAD51 assembly onto DNA or disrupt the stability of the pre-formed filament, thereby sensitizing cancer cells to treatment [PMID: 24413439]. Such inhibitors are of particular interest for treating tumors with "BRCAness" or as part of combination therapies to overcome chemoresistance [PMID: 30635554]. The filament's assembly is tightly regulated by mediator proteins like BRCA2, which facilitate the displacement of RPA from ssDNA to allow RAD51 loading [PMID: 20616063]. Disruption of this complex can lead to genomic instability, making it a double-edged sword in both cancer progression and therapy.

Other names

RAD51 nucleoprotein filamentRAD51 presynaptic filamentRAD51-ssDNA complexRAD51-ssDNA nucleoprotein filament

Inhibition of RAD51 polymerization onto single-stranded DNA, disruption of the nucleoprotein filament structure, or inhibition of RAD51-associated ATPase activity to prevent strand exchange [PMID: 22147242, 24413439].