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	OMIM: 600814 MGI: 1100512 HomoloGene: 4083 GeneCards: MRE11
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q21 Start 94,415,570 bp[1] End 94,493,885 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9|9 A2 Start 14,695,950 bp[2] End 14,748,419 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Achilles tendon oocyte secondary oocyte sural nerve monocyte rectum thymus hair follicle islet of Langerhans appendix Top expressed in ectoderm otic placode spermatid spermatocyte saccule primitive streak abdominal wall maxillary prominence seminiferous tubule yolk sac More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding manganese ion binding 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 nucleus cytoplasm nucleoplasm telomere chromosome Mre11 complex replication fork Biological process reciprocal meiotic recombination DNA recombination telomere maintenance via telomerase positive regulation of kinase activity mitotic intra-S DNA damage checkpoint signaling 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 homologous chromosome pairing at meiosis negative regulation of DNA endoreduplication double-strand break repair meiosis double-strand break repair via homologous recombination positive regulation of protein autophosphorylation cell population proliferation mitotic G2 DNA damage checkpoint signaling 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: 14.7 – 14.75 Mb PubMed search [3] [4]
Wikidata
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Double-strand break repair protein MRE11 is an enzyme that in humans is encoded by the MRE11 gene.^[5] The gene has been designated MRE11A to distinguish it from the pseudogene MRE11B that is nowadays named MRE11P1.

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 MRE11, 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 MRE11 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).^{[citation needed]} (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.^{[citation needed]} (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

MRE11 has been shown to interact with:

• ATM,^[11][12]
• BRCA1,^{[12][13][14][15]}
• Ku70,^[16]
• MDC1,^[17]
• NBN,^{[12][18][19][20][21]}
• Rad50,^{[12][13][16][18][22]} and
• TERF2.^[23]