SUMMARY PARAGRAPH for RAD54
Identified in a genetic screen for mutants that are sensitive to ionizing radiation, RAD54 is a member of the RAD52 epistasis group (7). Other members of this group include RAD50, RAD51, RAD52, RDH54, 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 in this epistasis group are defective in the repair of DNA damage caused by ionizing radiation and the alkylating agent methyl methanesulfonate (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 and 8).
RAD54 is not essential for viability in yeast and rad54 mutants are competent for repair via the single-strand annealing, break-induced replication, and non-homologous end joining repair pathways. However, these mutants are severely impaired in gene conversion and are more prone to chromosomal loss (reviewed in 9).
Rad54p interacts with Rad51p, ssDNA, and chromatin in order to stimulate homolgous DNA pairing (4 and reviewed in 9). Rad54p, a member of the SNF2 family of chromatin remodeling DNA-dependent ATPases, has been demonstrated to translocate along duplex DNA and redistribute the associated nucleosomes (reviewed in 10, 11, 12). Rad54p translocation also induces conformational change of closed-circular duplex DNA by generating both negative and positive supercoiled domains (13, 14). In addition, Rad54p facilitates Rad51p binding to ssDNA, stabilizes Rad51p nucleoprotein complexes, and stimulates Rad51p-mediated D-loop formation (reviewed in 5, 8, and 9).
Rad54p is also a dsDNA-dependent ATPase that is stimulated by Rad51p or Rad51p nucleoprotein complexes (12 and reviewed in 8, and 9). Though ATP hydrolysis is not required for mediating Rad51p binding to ssDNA, it is necessary for homologous DNA pairing and chromatin remodeling during Rad51p-ssDNA nucleoprotein filament strand invasion of dsDNA (15).
Rad54p has also been found to interact with Mus81p, an endonuclease involved in DNA repair (16). RAD54 expression is regulated by cell cycle, transcription occurring during late G1 phase, and is induced during meiosis and by DNA damaging agents (17, 18, 19, 20).
RAD54 homologs have been identified in S. pombe, Arabidopsis, Drosophila, chicken, mouse, and human (21, 22, 23, 24, 25). Mice lacking the murine homolog of RAD54 exhibit normal development and normal V(D)J and immunoglobulin class-switch recombination. However, like yeast, mouse embryonic cells carrying rad54 mutations do show increased sensitivity to DNA damaging agents as well as reduced rates of gene targeting (26 and reviewed in 5). Mutations in the human RAD54 homolog (OMIM) have been associated with various types of cancers (27).
Last updated: 2006-05-03