RAD51mediated

RAD51mediated refers to the set of processes in which RAD51 recombinase drives homologous recombination–based repair of DNA double-strand breaks. RAD51 is a DNA-binding protein that forms a helical nucleoprotein filament on single-stranded DNA, a state that requires ATP binding and hydrolysis for dynamic assembly and disassembly.

The repair pathway begins after DNA end resection creates single-stranded DNA, which is initially coated by RPA. Mediator proteins, most notably BRCA2 in humans, load RAD51 onto the resected DNA, displacing RPA to form the RAD51-ssDNA filament. The filament conducts an homology search and promotes strand invasion into the homologous duplex DNA, generating a displacement loop (D-loop). DNA synthesis extends the 3' end using the homologous template, and the resulting structures are resolved to produce crossover or non-crossover products. This process ensures accurate repair and maintenance of genome stability.

RAD51-mediated repair is essential during both mitotic and meiotic recombination. In meiosis, RAD51 cooperates with DMC1 to promote interhomolog recombination, contributing to genetic diversity and proper chromosome segregation. RAD51 activity is regulated by several cofactors and paralogs (RAD51B, RAD51C, RAD51D, XRCC2, XRCC3) that assist filament formation and stabilization, in addition to mediators like BRCA2. Dysfunctions in RAD51-mediated HR can lead to genomic instability and sensitivity to DNA-damaging agents, while overexpression in some cancers can contribute to therapy resistance.

Clinical and research relevance includes the use of RAD51 foci as a biomarker of HR activity and the exploration of RAD51 inhibitors to sensitize tumors to chemotherapy and radiotherapy.