RAD50/YNL250W Summary Help

Standard Name RAD50 1
Systematic Name YNL250W
Feature Type ORF, Verified
Description Subunit of MRX complex with Mre11p and Xrs2p; complex is involved in processing double-strand DNA breaks in vegetative cells, initiation of meiotic DSBs, telomere maintenance, and nonhomologous end joining; forms nuclear foci upon DNA replication stress (2, 3 and see Summary Paragraph)
Name Description RADiation sensitive
Chromosomal Location
ChrXIV:175410 to 179348 | ORF Map | GBrowse
Gbrowse
Genetic position: -170 cM
Gene Ontology Annotations All RAD50 GO evidence and references
  View Computational GO annotations for RAD50
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 1 genes
Resources
Classical genetics
null
reduction of function
Large-scale survey
null
repressible
Resources
521 total interaction(s) for 280 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 35
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 8
  • Co-fractionation: 1
  • Co-localization: 2
  • Co-purification: 2
  • Reconstituted Complex: 5
  • Two-hybrid: 20

Genetic Interactions
  • Dosage Growth Defect: 3
  • Dosage Lethality: 2
  • Dosage Rescue: 4
  • Negative Genetic: 92
  • Phenotypic Enhancement: 25
  • Phenotypic Suppression: 15
  • Positive Genetic: 10
  • Synthetic Growth Defect: 178
  • Synthetic Lethality: 105
  • Synthetic Rescue: 13

Resources
Expression Summary
histogram
Resources
Length (a.a.) 1,312
Molecular Weight (Da) 152,568
Isoelectric Point (pI) 5.92
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXIV:175410 to 179348 | ORF Map | GBrowse
SGD ORF map
Genetic position: -170 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..3939 175410..179348 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 SGDIDS000005194
SUMMARY PARAGRAPH for RAD50

Identified in a genetic screen for mutants that are sensitive to ionizing radiation (4) RAD50 is a member of the RAD52 epistasis group. Other members of this group include RAD51, RAD52, RAD54, 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 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 2 and 5).

Mre11p, Rad50p, and Xrs2p comprise the Mre11 complex. Mre11p/Rad50p/Xrs2p (MRX or RMX) association is stable with a predicted stoichiometry of 2:2:1, however, Rad50p and Xrs2p do not interact in the absence of Mre11p (6, 7). Complex functions include DNA binding, exonuclease and endonuclease activities, DNA unwinding, and DNA end recognition (8, 9, 10). In addition to the repair processes listed above, which are mostly dependent upon homologous recombination, the MRX complex also facilitates DSB repair via nonhomologous end-joining as well as introduction of DSBs in meiosis, detection of damaged DNA, DNA damage checkpoint activation, telomerase recruitment, and suppression of gross chromosomal rearrangements (reviewed in 2 and 5).

The Mre11 complex is conserved structurally and functionally from archaea to humans, but only the individual proteins Mre11p and Rad50p are widely and highly conserved; Xrs2p conservation is weak and its homologs are only present in eukaryotes (11, 12, 13 and reviewed in 14). In contrast to yeast mre11, rad50, and xrs2 null mutants, which are viable, loss of activity in any of the vertebrate homologs results in embryonic lethality or cell death (15, 16).

The Rad50p subunit belongs to the family of structural maintenance of chromosome (SMC) proteins (17). Like other proteins in this family, it has two globular ATPase domains at its N- and C-terminal ends separated by a long coiled-coil region made up of heptad repeats (17, 6, 18). The ATPase domains of Rad50p mediate the ATP-dependent activities of DNA binding and unwinding (19, 9). Additionally, the ATPase domains facilitate protein-protein interaction and stimulation of Mre11p nuclease activity (9, 20). Within the coiled-coil region is a conserved zinc-binding motif known as the ''RAD50 hook'' which is thought to mediate interaction between the coiled-coil region of two Rad50p molecules (18). The structural characteristics of Rad50p in addition to mutational studies of the complex suggest that one of the functions of MRX is to bridge gaps between DNA molecules and bring the ends of DSBs together (18, 21, and reviewed in 5).

Last updated: 2006-02-27 Contact SGD

References cited on this page View Complete Literature Guide for RAD50
1) Game, J.  (1985) Personal Communication, Mortimer Map Edition 9
2) 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
3) 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
4) Game JC and Mortimer RK  (1974) A genetic study of x-ray sensitive mutants in yeast. Mutat Res 24(3):281-92
5) Krogh BO and Symington LS  (2004) Recombination proteins in yeast. Annu Rev Genet 38():233-71
6) Usui T, et al.  (1998) Complex formation and functional versatility of Mre11 of budding yeast in recombination. Cell 95(5):705-16
7) Chen L, et al.  (2001) Promotion of Dnl4-catalyzed DNA end-joining by the Rad50/Mre11/Xrs2 and Hdf1/Hdf2 complexes. Mol Cell 8(5):1105-15
8) Paull TT and Gellert M  (1998) The 3' to 5' exonuclease activity of Mre 11 facilitates repair of DNA double-strand breaks. Mol Cell 1(7):969-79
9) Chen L, et al.  (2005) Effect of amino acid substitutions in the rad50 ATP binding domain on DNA double strand break repair in yeast. J Biol Chem 280(4):2620-7
10) Trujillo KM, et al.  (2003) Yeast xrs2 binds DNA and helps target rad50 and mre11 to DNA ends. J Biol Chem 278(49):48957-64
11) Dolganov GM, et al.  (1996) Human Rad50 is physically associated with human Mre11: identification of a conserved multiprotein complex implicated in recombinational DNA repair. Mol Cell Biol 16(9):4832-41
12) Sharples GJ and Leach DR  (1995) Structural and functional similarities between the SbcCD proteins of Escherichia coli and the RAD50 and MRE11 (RAD32) recombination and repair proteins of yeast. Mol Microbiol 17(6):1215-7
13) Carney JP, et al.  (1998) The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell 93(3):477-86
14) Connelly JC and Leach DR  (2002) Tethering on the brink: the evolutionarily conserved Mre11-Rad50 complex. Trends Biochem Sci 27(8):410-8
15) Tauchi H, et al.  (2002) Nbs1 is essential for DNA repair by homologous recombination in higher vertebrate cells. Nature 420(6911):93-8
16) Luo G, et al.  (1999) Disruption of mRad50 causes embryonic stem cell lethality, abnormal embryonic development, and sensitivity to ionizing radiation. Proc Natl Acad Sci U S A 96(13):7376-81
17) Anderson DE, et al.  (2001) Structure of the Rad50 x Mre11 DNA repair complex from Saccharomyces cerevisiae by electron microscopy. J Biol Chem 276(40):37027-33
18) Wiltzius JJ, et al.  (2005) The Rad50 hook domain is a critical determinant of Mre11 complex functions. Nat Struct Mol Biol 12(5):403-7
19) Raymond WE and Kleckner N  (1993) RAD50 protein of S.cerevisiae exhibits ATP-dependent DNA binding. Nucleic Acids Res 21(16):3851-6
20) Trujillo KM and Sung P  (2001) DNA structure-specific nuclease activities in the Saccharomyces cerevisiae Rad50*Mre11 complex. J Biol Chem 276(38):35458-64
21) Lobachev K, et al.  (2004) Chromosome fragmentation after induction of a double-strand break is an active process prevented by the RMX repair complex. Curr Biol 14(23):2107-12