Rad51

Rad51 is a protein in eukaryotes that functions as the central recombinase in homologous recombination, a high-fidelity DNA repair process. It is the eukaryotic homolog of bacterial RecA and is essential for repairing double-strand breaks and stalled replication forks during both mitotic and meiotic cell cycles. Rad51 binds to single-stranded DNA generated by end resection and forms presynaptic nucleoprotein filaments that promote homology search and strand invasion into an intact duplex, leading to the formation of a displacement loop and subsequent strand exchange.

Rad51 activity depends on mediator and accessory proteins. In cells, RPA coats the exposed ssDNA, and mediator proteins such as BRCA2 (with partners PALB2 and others) help load Rad51 onto DNA and displace RPA. Rad51 filaments interact with the RAD51 paralogs—RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3—that stabilize filaments and promote progression of recombination. Its activity is regulated by cell cycle cues and post-translational modifications, including phosphorylation by ATM/ATR in response to DNA damage.

In meiosis, Rad51 supports homologous recombination necessary for crossing over, while the related Dmc1 recombinase is also involved in many organisms. In humans, defects in RAD51 or its paralogs are associated with genomic instability and increased cancer risk, and complete loss is lethal in animal models, underscoring its essential role in genome maintenance.

Rad51 has become a target in cancer therapy research, with strategies to exploit HR defects in tumors or to inhibit Rad51 function to sensitize cells to DNA-damaging agents. The RAD51 pathway is often studied using reporter assays for homologous recombination efficiency.

Discovery and naming: The gene was identified in yeast as RAD51 and later shown to be the functional vertebrate homolog of RecA.