XRS2/YDR369C Summary Help

Standard Name XRS2 1, 2
Systematic Name YDR369C
Feature Type ORF, Verified
Description Protein required for DNA repair; component of the Mre11 complex, which is involved in double strand breaks, meiotic recombination, telomere maintenance, and checkpoint signaling (3, 4, 5 and see Summary Paragraph)
Name Description X-Ray Sensitive
Chromosomal Location
ChrIV:1217580 to 1215016 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Genetic position: 211 cM
Gene Ontology Annotations All XRS2 GO evidence and references
  View Computational GO annotations for XRS2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 2 genes
Resources
Classical genetics
null
Large-scale survey
null
overexpression
Resources
462 total interaction(s) for 233 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 18
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 17
  • Biochemical Activity: 1
  • Co-purification: 2
  • Far Western: 1
  • Reconstituted Complex: 5
  • Two-hybrid: 13

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Lethality: 1
  • Dosage Rescue: 3
  • Negative Genetic: 175
  • Phenotypic Enhancement: 12
  • Phenotypic Suppression: 5
  • Positive Genetic: 5
  • Synthetic Growth Defect: 145
  • Synthetic Lethality: 55
  • Synthetic Rescue: 2

Resources
Expression Summary
histogram
Resources
Length (a.a.) 854
Molecular Weight (Da) 96,364
Isoelectric Point (pI) 8.31
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrIV:1217580 to 1215016 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Genetic position: 211 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..2565 1217580..1215016 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 | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000002777
SUMMARY PARAGRAPH for XRS2

Identified in a genetic screen for mutants that are sensitive to ionizing radiation, XRS2 is a member of the RAD52 epistasis group (3 and references contained therein). Other members of this group include RAD50, RAD51, RAD52, RAD54, RDH54, RAD55, RAD57, RAD59, and MRE11. 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 6 and 7).

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 (5, 8). Complex functions include DNA binding, exonuclease and endonuclease activities, DNA unwinding, and DNA end recognition (9, 10, 11). 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 6 and 7).

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 (12, 13, 14 and reviewed in 15). 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 (16, 17).

Mutations in the functional homolog of XRS2, human NBS1, have been linked to the autosomal recessive disorder Nijmegen Breakage Syndrome (OMIM). This disease is characterized by the molecular features of chromosomal instability and increased sensitivity to radiation, and the clinical phenotypes of microcephaly, growth retardation, immunodeficiency, and predisposition to cancer (reviewed in 18).

Xrs2p binds DNA in a structure-specific manner and has been shown to be important for targeting the MRX complex to DNA ends (11). The N-terminal domain contains a conserved forkhead-associated domain that is not required for any of the major MRX complex functions in yeast (19). The C-terminal domain contains both Mre11p and Tel1p binding sites that mediate translocation of Mre11p to the nucleus and Tel1p phosphorylation of Xrs2p (20). Xrs2p is also able to stimulate Mre11p exonuclease activity (11) and Xrs2p interaction with Lif1p facilitates MRX complex association with the DNA ligase Dnl4p (8).

Last updated: 2006-02-27 Contact SGD

References cited on this page View Complete Literature Guide for XRS2
1) Korolev, V.  (1992) Personal Communication, Mortimer Map Edition 11
2) Zakharov, I.A.  (1989) Personal Communication, Mortimer Map Edition 10
3) Ivanov EL, et al.  (1992) XRS2, a DNA repair gene of Saccharomyces cerevisiae, is needed for meiotic recombination. Genetics 132(3):651-64
4) Bressan DA, et al.  (1999) The Mre11-Rad50-Xrs2 protein complex facilitates homologous recombination-based double-strand break repair in Saccharomyces cerevisiae. Mol Cell Biol 19(11):7681-7
5) Usui T, et al.  (1998) Complex formation and functional versatility of Mre11 of budding yeast in recombination. Cell 95(5):705-16
6) 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
7) Krogh BO and Symington LS  (2004) Recombination proteins in yeast. Annu Rev Genet 38():233-71
8) 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
9) 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
10) 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
11) 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
12) 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
13) 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
14) 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
15) Connelly JC and Leach DR  (2002) Tethering on the brink: the evolutionarily conserved Mre11-Rad50 complex. Trends Biochem Sci 27(8):410-8
16) Tauchi H, et al.  (2002) Nbs1 is essential for DNA repair by homologous recombination in higher vertebrate cells. Nature 420(6911):93-8
17) 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
18) Tauchi H  (2000) Positional cloning and functional analysis of the gene responsible for Nijmegen breakage syndrome, NBS1. J Radiat Res (Tokyo) 41(1):9-17
19) Shima H, et al.  (2005) Isolation and characterization of novel xrs2 mutations in Saccharomyces cerevisiae. Genetics 170(1):71-85
20) Usui T, et al.  (2001) A DNA damage response pathway controlled by Tel1 and the Mre11 complex. Mol Cell 7(6):1255-66