SUMMARY PARAGRAPH for RAD52
Identified in a genetic screen for mutants that are sensitive to ionizing radiation (6), RAD52 is a member of the RAD52 epistasis group. Other members of this group include RAD50, RAD51, RAD54, RAD55, RAD57, RAD59, MRE11, and XRS2. All members of the RAD52 epistasis group are involved in the repair of double-stranded breaks (DSBs) in DNA. Mutants are defective in the repair of DNA damage cause by ionizing radiation and MMS and in the maintenance of telomere length, in mitotic and meiotic recombination, and in mating-type switching because DSB intermediates are involved in these processes (reviewed in 7, 4). Of all the members of the RAD52 epistasis group, the absence of RAD52 confers the most severe defects because it is involved in multiple pathways of repairing DSBs. RAD52 plays a role in the RAD51-dependent double-strand break repair (DSBR) pathway, known as synthesis-dependent strand annealing (SDSA) as well as in RAD51-independent DSBR pathways, known as break-induced replication (BIR) and single-strand annealing (SSA) (review in 7).
Biochemical studies of Rad52p give insight into its role in multiple DSBR pathways. Rad52p stimulates the Rad51p recombinase activty (8, 2, 9). Rad52p interacts with Rad51p and Replication Protein A (RPA), which is comprised of Rfa1p, Rfa2p, and Rfa3p (10, 11). These interactions may facilitate the formation of Rad51p:single-stranded DNA nucleoprotein filaments in the presence of RPA (12, 13). In addition, Rad52p anneals complementary strands of ssDNA (3, 14). Rad52p also interacts with Rad59p, an interaction that may be important in its Rad51-independent DSB repair pathways (15).
Although RAD52 is expressed throughout the cell cycle, it is induced during meiosis and in response to DNA damaging agents (16, 17). A Rad52p-GFP fusion forms nuclear foci in the absence and presence of DNA damaging agents (18). Electron microscopic studies of purified yeast Rad52p shows that it forms a ring structure but it is not clear how Rad52p binds DNA (14).
Orthologs of RAD52 have been identified in many organisms, including chicken, S. pombe, mice, and humans (19, 20, 21). In contrast to the situation in yeast, the absence of RAD52 in higher eukaryotes does not result in a severe phenotype (22, 23) because there are additional functionally redundant proteins (24, reviewed in 25).
Last updated: 2003-01-06