RAD54/YGL163C Summary Help

Standard Name RAD54 1, 2
Systematic Name YGL163C
Alias XRS1
Feature Type ORF, Verified
Description DNA-dependent ATPase that stimulates strand exchange; modifies the topology of double-stranded DNA; involved in the recombinational repair of double-strand breaks in DNA during vegetative growth and meiosis; member of the SWI/SNF family of DNA translocases; forms nuclear foci upon DNA replication stress (3, 4, 5, 6, 7 and see Summary Paragraph)
Name Description RADiation sensitive
Chromosomal Location
ChrVII:196403 to 193707 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Genetic position: -111 cM
Gene Ontology Annotations All RAD54 GO evidence and references
  View Computational GO annotations for RAD54
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 6 genes
Resources
Classical genetics
null
reduction of function
Large-scale survey
null
Resources
374 total interaction(s) for 191 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 4
  • Affinity Capture-Western: 7
  • Biochemical Activity: 1
  • Reconstituted Complex: 13
  • Two-hybrid: 9

Genetic Interactions
  • Dosage Lethality: 1
  • Dosage Rescue: 4
  • Negative Genetic: 105
  • Phenotypic Enhancement: 14
  • Phenotypic Suppression: 5
  • Positive Genetic: 22
  • Synthetic Growth Defect: 131
  • Synthetic Lethality: 40
  • Synthetic Rescue: 18

Resources
Expression Summary
histogram
Resources
Length (a.a.) 898
Molecular Weight (Da) 101,753
Isoelectric Point (pI) 9.63
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrVII:196403 to 193707 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Genetic position: -111 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..2697 196403..193707 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000003131
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 (8). 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 9).

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 10).

Rad54p interacts with Rad51p, ssDNA, and chromatin in order to stimulate homolgous DNA pairing (4 and reviewed in 10). 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 11, 12, 13). Rad54p translocation also induces conformational change of closed-circular duplex DNA by generating both negative and positive supercoiled domains (14, 15). In addition, Rad54p facilitates Rad51p binding to ssDNA, stabilizes Rad51p nucleoprotein complexes, and stimulates Rad51p-mediated D-loop formation (reviewed in 5, 9, and 10).

Rad54p is also a dsDNA-dependent ATPase that is stimulated by Rad51p or Rad51p nucleoprotein complexes (13 and reviewed in 9, and 10). 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 (16).

Rad54p has also been found to interact with Mus81p, an endonuclease involved in DNA repair (17). RAD54 expression is regulated by cell cycle, transcription occurring during late G1 phase, and is induced during meiosis and by DNA damaging agents (18, 19, 20, 21).

RAD54 homologs have been identified in S. pombe, Arabidopsis, Drosophila, chicken, mouse, and human (22, 23, 24, 25, 26). 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 (27 and reviewed in 5). Mutations in the human RAD54 homolog (OMIM) have been associated with various types of cancers (28).

Last updated: 2006-05-03 Contact SGD

References cited on this page View Complete Literature Guide for RAD54
1) Dowling, E.L.  (1985) Ph.D. thesis
2) Game, J.  (1985) Personal Communication, Mortimer Map Edition 9
3) Petukhova G, et al.  (1999) Yeast Rad54 promotes Rad51-dependent homologous DNA pairing via ATP hydrolysis-driven change in DNA double helix conformation. J Biol Chem 274(41):29453-62
4) Clever B, et al.  (1997) Recombinational repair in yeast: functional interactions between Rad51 and Rad54 proteins. EMBO J 16(9):2535-44
5) Symington LS  (2002) Role of RAD52 epistasis group genes in homologous recombination and double-strand break repair. Microbiol Mol Biol Rev 66(4):630-70, table of contents
6) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
7) Busygina V, et al.  (2013) Functional attributes of the Saccharomyces cerevisiae meiotic recombinase Dmc1. DNA Repair (Amst) 12(9):707-12
8) Game JC and Mortimer RK  (1974) A genetic study of x-ray sensitive mutants in yeast. Mutat Res 24(3):281-92
9) Krogh BO and Symington LS  (2004) Recombination proteins in yeast. Annu Rev Genet 38():233-71
10) Dudas A and Chovanec M  (2004) DNA double-strand break repair by homologous recombination. Mutat Res 566(2):131-67
11) Eisen JA, et al.  (1995) Evolution of the SNF2 family of proteins: subfamilies with distinct sequences and functions. Nucleic Acids Res 23(14):2715-23
12) Petukhova G, et al.  (1998) Catalysis of homologous DNA pairing by yeast Rad51 and Rad54 proteins. Nature 393(6680):91-4
13) Alexeev A, et al.  (2003) Rad54 protein possesses chromatin-remodeling activity stimulated by the Rad51-ssDNA nucleoprotein filament. Nat Struct Biol 10(3):182-6
14) Mazin AV, et al.  (2000) Rad54 protein is targeted to pairing loci by the Rad51 nucleoprotein filament. Mol Cell 6(3):583-92
15) Van Komen S, et al.  (2000) Superhelicity-driven homologous DNA pairing by yeast recombination factors Rad51 and Rad54. Mol Cell 6(3):563-72
16) Wolner B and Peterson CL  (2005) ATP-dependent and ATP-independent roles for the Rad54 chromatin remodeling enzyme during recombinational repair of a DNA double strand break. J Biol Chem 280(11):10855-60
17) Interthal H and Heyer WD  (2000) MUS81 encodes a novel helix-hairpin-helix protein involved in the response to UV- and methylation-induced DNA damage in Saccharomyces cerevisiae. Mol Gen Genet 263(5):812-27
18) Johnston LH and Johnson AL  (1995) The DNA repair genes RAD54 and UNG1 are cell cycle regulated in budding yeast but MCB promoter elements have no essential role in the DNA damage response. Nucleic Acids Res 23(12):2147-52
19) Cole GM, et al.  (1989) Two DNA repair and recombination genes in Saccharomyces cerevisiae, RAD52 and RAD54, are induced during meiosis. Mol Cell Biol 9(7):3101-4
20) Cole GM and Mortimer RK  (1989) Failure to induce a DNA repair gene, RAD54, in Saccharomyces cerevisiae does not affect DNA repair or recombination phenotypes. Mol Cell Biol 9(8):3314-22
21) Cole GM, et al.  (1987) Regulation of RAD54- and RAD52-lacZ gene fusions in Saccharomyces cerevisiae in response to DNA damage. Mol Cell Biol 7(3):1078-84
22) Muris DF, et al.  (1996) Isolation of the Schizosaccharomyces pombe RAD54 homologue, rhp54+, a gene involved in the repair of radiation damage and replication fidelity. J Cell Sci 109 ( Pt 1)():73-81
23) Shaked H, et al.  (2006) Involvement of the Arabidopsis SWI2/SNF2 chromatin remodeling gene family in DNA damage response and recombination. Genetics 173(2):985-94
24) Kooistra R, et al.  (1997) The Drosophila melanogaster RAD54 homolog, DmRAD54, is involved in the repair of radiation damage and recombination. Mol Cell Biol 17(10):6097-104
25) Bezzubova O, et al.  (1997) Reduced X-ray resistance and homologous recombination frequencies in a RAD54-/- mutant of the chicken DT40 cell line. Cell 89(2):185-93
26) Kanaar R, et al.  (1996) Human and mouse homologs of the Saccharomyces cerevisiae RAD54 DNA repair gene: evidence for functional conservation. Curr Biol 6(7):828-38
27) Essers J, et al.  (1997) Disruption of mouse RAD54 reduces ionizing radiation resistance and homologous recombination. Cell 89(2):195-204
28) Smirnova M, et al.  (2004) Effects of tumor-associated mutations on Rad54 functions. J Biol Chem 279(23):24081-8