DNA repair protein RAD51 (RAD51)

DNA repair protein RAD51 is a central recombinase in human cells, essential for homologous recombination (HR), a high-fidelity pathway for repairing DNA double-strand breaks (DSBs) and protecting stalled replication forks (UniProt: P25454). It functions by polymerizing onto single-stranded DNA to form a nucleoprotein filament that catalyzes the search for a homologous DNA sequence and promotes strand invasion (PMID: 29075059). In clinical oncology, RAD51 is frequently overexpressed in various aggressive tumors, where it facilitates the repair of therapy-induced DNA damage, leading to resistance against ionizing radiation and cross-linking chemotherapy agents like cisplatin (PMID: 30604323). Consequently, RAD51 is a significant therapeutic target; inhibitors like CYT-0851 have entered clinical trials to sensitize resistant tumors or exploit synthetic lethality in cells with pre-existing DNA repair deficiencies (NCT03992430). However, because RAD51 is also vital for the maintenance of genomic stability in normal proliferating tissues and during meiosis, therapeutic strategies must carefully balance efficacy against potential systemic toxicities.

Other names

RAD51 homolog AHsRad51RECARAD51AFanconi anemia complementation group RFANCR

Inhibition of RAD51 nucleoprotein filament formation and strand exchange activity to impair homologous recombination-mediated DNA repair.