SUMMARY PARAGRAPH for RAD51
Identified in a genetic screen for mutants that are sensitive to ionizing radiation (4), RAD51 is a member of the RAD52 epistasis group. Other members of this group include RAD50, RAD52, 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 caused by ionizing radiation and MMS, 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 5, 3).
A rad51 deletion mutation is not lethal in S. cerevisiae because DSBs can be repaired by multiple pathways. RAD51 is only involved in DSB repair via synthesis-dependent strand annealing (SDSA) and is not involved in DSB repair via break-induced replication (BIR) or single-strand annealing (SSA) (reviewed in 5).
The function of Rad51p was predicted by its structural homology to the bacterial DNA repair protein RecA and the T4 phage protein UvsX (2, 6, 7, reviewed in 8). Rad51p is a recombinase ; it binds DNA (2) and catalyzes the identification and exchange of homologous sequences between a single-strand DNA (ssDNA) molecule and a double-stranded DNA (dsDNA) molecule (1). Rad51p interacts with itself and other members of the RAD52 epistasis group: Rad52p, the Rad55p-Rad57p heterodimer, Rad54p, and Rdh54p/Tid1p (2, 9, 10, 11). These interacting proteins stimulate the assembly of Rad51p onto ssDNA and its recombinase activity (12, 13, 14, 15, 16, 17).
The role of RAD51 in meiosis is complicated by the presence of the meiosis-specific RecA homolog DMC1 (2, 18, 19). Coordination of RAD51 with DMC1 and other members of the RAD52 epistasis group is required to convert DSBs into Holliday junctions (a recombination intermediate) and for full levels of recombinant products (20, 18, 21, 22).
Although RAD51 is expressed throughout the cell cycle, it is induced during meiosis and in response to DNA damaging agents (2, 23). Rad51p forms discrete foci on chromosomes that can be detected cytologically during mitosis and meiosis (review in 24).
Orthologs of RAD51 have been identified in many organisms, including humans, mice, chicken, and X. laevis (25, 26, 27, 28). In contrast to the situation in yeast, the absence of rad51 in higher eukaryotes results in embryonic lethality or cell death (29, 30, 31).
Last updated: 2001-01-03