RAD52, or Mammalian Radiation Sensitive 52, is a key gene in eukaryotes involved in multiple DNA metabolic pathways. It is crucial for homologous recombination (HR), a high-fidelity pathway for repairing damaged double-stranded DNA. RAD52 also contributes to backup DNA repair pathways in HR-deficient cancer cells, such as break-induced replication (BIR), single-strand annealing, and RNA-mediated repair of DNA [1].

Knockouts of mammalian RAD52 initially lacked discernable phenotypes, but recent studies have shown its significance. In HR-deficient cells, RAD52 deficiency is synthetically lethal with defects in BRCA genes, making it an attractive therapeutic target for BRCA-deficient tumors [1,2]. In Cyclin E1-overexpressing cells, RAD52-dependent mitotic DNA synthesis is required for genome stability, and inactivation of RAD52 enhances mitotic aberrations and persistent DNA damage [3]. Also, in cells with replication stress, RAD52 has multiple activities to protect genome stability at common fragile sites, which are often associated with cancer-related DNA breakpoints [4].

In conclusion, RAD52 plays essential roles in DNA repair and genome maintenance. Its functions are particularly crucial in HR-deficient cells and in cells experiencing replication stress. The study of RAD52 using gene knockout models has revealed its potential as a therapeutic target, especially in BRCA-deficient cancers, contributing to a better understanding of cancer biology and the development of anti-cancer therapies.