MRE11/YMR224C Summary Help

Standard Name MRE11 1
Systematic Name YMR224C
Alias RAD58 , XRS4 , NGS1
Feature Type ORF, Verified
Description Nuclease subunit of the MRX complex with Rad50p and Xrs2p; complex functions in repair of DNA double-strand breaks and in telomere stability; Mre11p associates with Ser/Thr-rich ORFs in premeiotic phase; nuclease activity required for MRX function; widely conserved; forms nuclear foci upon DNA replication stress (2, 3, 4, 5, 6 and see Summary Paragraph)
Name Description Meiotic REcombination 7
Chromosomal Location
ChrXIII:720653 to 718575 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All MRE11 GO evidence and references
  View Computational GO annotations for MRE11
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 3 genes
Resources
Classical genetics
null
reduction of function
unspecified
Large-scale survey
null
unspecified
Resources
792 total interaction(s) for 407 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 12
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 28
  • Co-fractionation: 1
  • Co-localization: 3
  • Co-purification: 2
  • Far Western: 2
  • Reconstituted Complex: 9
  • Two-hybrid: 25

Genetic Interactions
  • Dosage Growth Defect: 3
  • Dosage Lethality: 1
  • Dosage Rescue: 7
  • Negative Genetic: 234
  • Phenotypic Enhancement: 51
  • Phenotypic Suppression: 28
  • Positive Genetic: 11
  • Synthetic Growth Defect: 154
  • Synthetic Lethality: 208
  • Synthetic Rescue: 11

Resources
Expression Summary
histogram
Resources
Length (a.a.) 692
Molecular Weight (Da) 77,650
Isoelectric Point (pI) 5.71
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXIII:720653 to 718575 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..2079 720653..718575 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 SGDIDS000004837
SUMMARY PARAGRAPH for MRE11

Identified in separate screens for mutants sensitive to ionizing radiation and alkylating agents and defective in meiotic recombination, MRE11 is a member of the RAD52 epistasis group (8 and references therein, 9, 7). Other members of this group include RAD50, RAD51, RAD52, RAD54, RDH54, RAD55, RAD57, RAD59, 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 10 and 11).

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 (12, 13). Complex functions include DNA binding, exonuclease and endonuclease activities, DNA unwinding, and DNA end recognition (14, 15, 16). 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 10 and 11).

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 (17, 18, 19 and reviewed in 20). 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 (21, 22).

Mutations in the human homolog of MRE11 have been linked to the disease ataxia-telangiectasia-like disorder (OMIM), which is characterized by chromosomal instability, increased sensitivity to radiation, and progressive cerebellar degeneration (23 and references contained therein).

The nuclease activity of the MRX complex is mediated by the Mre11p subunit. Mre11p has both a 3'-5' exonuclease activity and a structurally specific endonuclease activity, which are manganese-dependent and localized to the N-terminus of the protein (24, 25). The N-terminal portion of Mre11p, which contains motifs shared by the phosphoesterase family, is also important for maintaining interaction with the other complex subunits, Xrs2p and Rad50p (12, 26). Xrs2p stimulates the exonuclease activity of Mre11p while Rad50p enhances the endonuclease activity (16, 25). The Mre11p C-terminus mediates DNA binding to both single- and double-stranded DNA in a structure- and sequence-specific manner (27, 12, 24).

Last updated: 2006-02-27 Contact SGD

References cited on this page View Complete Literature Guide for MRE11
1) Johzuka K and Ogawa H  (1995) Interaction of Mre11 and Rad50: two proteins required for DNA repair and meiosis-specific double-strand break formation in Saccharomyces cerevisiae. Genetics 139(4):1521-32
2) D'Amours D and Jackson SP  (2002) The Mre11 complex: at the crossroads of dna repair and checkpoint signalling. Nat Rev Mol Cell Biol 3(5):317-27
3) Moncalian G, et al.  (2004) The rad50 signature motif: essential to ATP binding and biological function. J Mol Biol 335(4):937-51
4) Lewis LK, et al.  (2004) Role of the nuclease activity of Saccharomyces cerevisiae Mre11 in repair of DNA double-strand breaks in mitotic cells. Genetics 166(4):1701-13
5) Bowen S and Wheals AE  (2006) Ser/Thr-rich domains are associated with genetic variation and morphogenesis in Saccharomyces cerevisiae. Yeast 23(8):633-40
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) Ajimura M, et al.  (1993) Identification of new genes required for meiotic recombination in Saccharomyces cerevisiae. Genetics 133(1):51-66
8) Chepurnaya OV, et al.  (1995) RAD58 (XRS4)--a new gene in the RAD52 epistasis group. Curr Genet 28(3):274-9
9) Nisson PE and Lawrence CW  (1986) The isolation and characterization of an alkylating-agent-sensitive yeast mutant, ngs1. Mutat Res 165(3):129-37
10) 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
11) Krogh BO and Symington LS  (2004) Recombination proteins in yeast. Annu Rev Genet 38():233-71
12) Usui T, et al.  (1998) Complex formation and functional versatility of Mre11 of budding yeast in recombination. Cell 95(5):705-16
13) 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
14) 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
15) 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
16) 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
17) 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
18) 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
19) 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
20) Connelly JC and Leach DR  (2002) Tethering on the brink: the evolutionarily conserved Mre11-Rad50 complex. Trends Biochem Sci 27(8):410-8
21) Tauchi H, et al.  (2002) Nbs1 is essential for DNA repair by homologous recombination in higher vertebrate cells. Nature 420(6911):93-8
22) 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
23) Stewart GS, et al.  (1999) The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder. Cell 99(6):577-87
24) Furuse M, et al.  (1998) Distinct roles of two separable in vitro activities of yeast Mre11 in mitotic and meiotic recombination. EMBO J 17(21):6412-25
25) 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
26) Krogh BO, et al.  (2005) Mutations in Mre11 phosphoesterase motif I that impair Saccharomyces cerevisiae Mre11-Rad50-Xrs2 complex stability in addition to nuclease activity. Genetics 171(4):1561-70
27) Ghosal G and Muniyappa K  (2005) Saccharomyces cerevisiae Mre11 is a high-affinity G4 DNA-binding protein and a G-rich DNA-specific endonuclease: implications for replication of telomeric DNA. Nucleic Acids Res 33(15):4692-703