Brstjjy

MRE11
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3T1I
Identifiers
Aliases	MRE11, ATLD, HNGS1, MRE11B, MRE11A, MRE11 homolog A, double strand break repair nuclease, MRE11 homolog, double strand break repair nuclease
External IDs	MGI: 1100512 HomoloGene: 4083 GeneCards: MRE11
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q21 Start 94,415,578 bp[1] End 94,493,908 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9|9 A2 Start 14,784,654 bp[2] End 14,837,123 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • DNA binding • manganese ion binding • ATP-dependent DNA helicase activity • single-stranded DNA endodeoxyribonuclease activity • protein C-terminus binding • protein binding • 3'-5' exonuclease activity • nuclease activity • endonuclease activity • double-stranded DNA binding • endodeoxyribonuclease activity • exonuclease activity • hydrolase activity • cadherin binding • identical protein binding • 3'-5'-exodeoxyribonuclease activity • 5'-3' exonuclease activity Cellular component • site of double-strand break • cytosol • PML body • nuclear chromosome, telomeric region • cell nucleus • cytoplasm • nucleoplasm • chromosome, telomeric region • chromosome • Mre11 complex • replication fork Biological process • reciprocal meiotic recombination • DNA recombination • telomere maintenance via telomerase • positive regulation of kinase activity • intra-S DNA damage checkpoint • telomeric 3' overhang formation • negative regulation of apoptotic process • chromosome organization • sister chromatid cohesion • cellular response to DNA damage stimulus • positive regulation of telomere maintenance • DNA duplex unwinding • synapsis • negative regulation of DNA endoreduplication • double-strand break repair • meiotic cell cycle • double-strand break repair via homologous recombination • positive regulation of protein autophosphorylation • cell proliferation • mitotic G2 DNA damage checkpoint • viral process • double-strand break repair via nonhomologous end joining • positive regulation of type I interferon production • regulation of mitotic recombination • DNA repair • nucleic acid phosphodiester bond hydrolysis • DNA double-strand break processing • strand displacement • DNA replication • DNA synthesis involved in DNA repair • regulation of signal transduction by p53 class mediator • telomere maintenance • meiotic DNA double-strand break formation • mitochondrial double-strand break repair via homologous recombination • DNA strand resection involved in replication fork processing Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4361	17535
Ensembl	ENSG00000020922	ENSMUSG00000031928
UniProt	P49959	Q61216
RefSeq (mRNA)	NM_005590 NM_005591 NM_001330347	NM_018736 NM_001310728
RefSeq (protein)	NP_001317276 NP_005581 NP_005582	NP_001297657 NP_061206
Location (UCSC)	Chr 11: 94.42 – 94.49 Mb	Chr 9: 14.78 – 14.84 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Double-strand break repair protein MRE11A is a protein that in humans is encoded by the MRE11A gene.^[5]

Function

This gene encodes a nuclear protein involved in homologous recombination, telomere length maintenance, and DNA double-strand break repair. By itself, the protein has 3' to 5' exonuclease activity and endonuclease activity. The protein forms a complex with the RAD50 homolog; this complex is required for nonhomologous joining of DNA ends and possesses increased single-stranded DNA endonuclease and 3' to 5' exonuclease activities. In conjunction with a DNA ligase, this protein promotes the joining of noncomplementary ends in vitro using short homologies near the ends of the DNA fragments. This gene has a pseudogene on chromosome 3. Alternative splicing of this gene results in two transcript variants encoding different isoforms.^[6]

Orthologs

Mre11, an ortholog of human MRE11A, occurs in the prokaryote archaeon Sulfolobus acidocaldarius.^[7] In this organism the Mre11 protein interacts with the Rad50 protein and appears to have an active role in the repair of DNA damages experimentally introduced by gamma radiation.^[7] Similarly, during meiosis in the eukaryotic protist Tetrahymena Mre11 is required for repair of DNA damages, in this case double-strand breaks,^[8] by a process that likely involves homologous recombination. These observations suggest that human MRE11A is descended from prokaryotic and protist ancestral Mre11 proteins that served a role in early processes for repairing DNA damage.

Overexpression in cancer

MRE11 has a role in microhomology-mediated end joining (MMEJ) repair of double strand breaks. It is one of 6 enzymes required for this error prone DNA repair pathway.^[9] MRE11 is over-expressed in breast cancers.^[10]

Cancers are very often deficient in expression of one or more DNA repair genes, but over-expression of a DNA repair gene is less usual in cancer. For instance, at least 36 DNA repair enzymes, when mutationally defective in germ line cells, cause increased risk of cancer (hereditary cancer syndromes).^[11] (Also see DNA repair-deficiency disorder.) Similarly, at least 12 DNA repair genes have frequently been found to be epigenetically repressed in one or more cancers.^[11] (See also Epigenetically reduced DNA repair and cancer.) Ordinarily, deficient expression of a DNA repair enzyme results in increased un-repaired DNA damages which, through replication errors (translesion synthesis), lead to mutations and cancer. However, MRE11 mediated MMEJ repair is highly inaccurate, so in this case, over-expression, rather than under-expression, apparently leads to cancer.

Interactions

MRE11A has been shown to interact with:

• 
  ATM,^[12][13]
  


• 
  BRCA1,^{[13][14][15][16]}
  


• 
  Ku70,^[17]
  


• 
  MDC1,^[18]
  


• 
  NBN,^{[13][19][20][21][22]}
  


• 
  Rad50,^{[13][14][17][19][23]} and


• 
  TERF2.^[24]
  

See also

• Homologous recombination

References

Further reading