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Gene Review

MRE11A  -  MRE11 meiotic recombination 11 homolog A...

Homo sapiens

Synonyms: ATLD, Double-strand break repair protein MRE11A, HNGS1, MRE11, MRE11 homolog 1, ...
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Disease relevance of MRE11A


Psychiatry related information on MRE11A


High impact information on MRE11A

  • In contrast, concomitant interference with Nbs1-Mre11 and the Chk2-Cdc25A-Cdk2 pathways entirely abolishes inhibition of DNA synthesis induced by ionizing radiation, resulting in complete RDS analogous to that caused by defective ATM [7].
  • The Mre11 complex is required for repair of hairpin-capped double-strand breaks and prevention of chromosome rearrangements [8].
  • Our results suggest an additional role for the Mre11 complex in maintaining genome stability [8].
  • The NBSp26 protein is not physically associated with the MRE11 complex, whereas the p70 species is physically associated with it [9].
  • To clarify functions of the Mre11/Rad50 (MR) complex in DNA double-strand break repair, we report Pyrococcus furiosus Mre11 crystal structures, revealing a protein phosphatase-like, dimanganese binding domain capped by a unique domain controlling active site access [10].

Chemical compound and disease context of MRE11A


Biological context of MRE11A


Anatomical context of MRE11A


Associations of MRE11A with chemical compounds


Physical interactions of MRE11A

  • The Mre11 complex is required for ATM activation and the G2/M checkpoint [25].
  • Linkage between Werner syndrome protein and the Mre11 complex via Nbs1 [26].
  • Consequently, the FHA/BRCT domain is likely to have a crucial role for both binding to histone and for relocalization of hMRE11/hRAD50 nuclease complex to the vicinity of DNA damage [27].
  • Nbs1 is required for the Mre11 complex promotion of WRN helicase activity [26].
  • Here, we discuss how WRN, the MRE11 complex and the ATR kinase could work together in response to replication blockage to avoid DNA replication fork collapse and genome instability [28].

Enzymatic interactions of MRE11A


Co-localisations of MRE11A

  • In response to gamma-irradiation or mitomycin C, WRN leaves the nucleoli and co-localizes with the Mre11 complex in the nucleoplasm [26].

Regulatory relationships of MRE11A

  • Downregulation of MDC1 expression by small interfering RNA yields a radio-resistant DNA synthesis (RDS) phenotype and prevents ionizing radiation-induced focus formation by the MRE11 complex [30].
  • NBS cells are also deficient for radiation-induced nuclear foci containing Mre11, while those with Rad51 are unaffected [31].
  • New data suggest that the Mre11 complex can directly activate the ATM checkpoint kinase at DNA breaks [32].
  • Alternatively, the elevated yield of Mre11 foci positive cells following wortmannin treatment may reflect an overall perturbation to the signaling cascades regulated by wortmannin-sensitive PI3 related kinases [33].
  • ATM and ATR promote Mre11 dependent restart of collapsed replication forks and prevent accumulation of DNA breaks [34].

Other interactions of MRE11A


Analytical, diagnostic and therapeutic context of MRE11A


  1. Characterization of the linkage disequilibrium structure and identification of tagging-SNPs in five DNA repair genes. Allen-Brady, K., Camp, N.J. BMC Cancer (2005) [Pubmed]
  2. The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder. Stewart, G.S., Maser, R.S., Stankovic, T., Bressan, D.A., Kaplan, M.I., Jaspers, N.G., Raams, A., Byrd, P.J., Petrini, J.H., Taylor, A.M. Cell (1999) [Pubmed]
  3. Identification and functional consequences of a novel MRE11 mutation affecting 10 Saudi Arabian patients with the ataxia telangiectasia-like disorder. Fernet, M., Gribaa, M., Salih, M.A., Seidahmed, M.Z., Hall, J., Koenig, M. Hum. Mol. Genet. (2005) [Pubmed]
  4. Defective Mre11-dependent Activation of Chk2 by Ataxia Telangiectasia Mutated in Colorectal Carcinoma Cells in Response to Replication-dependent DNA Double Strand Breaks. Takemura, H., Rao, V.A., Sordet, O., Furuta, T., Miao, Z.H., Meng, L., Zhang, H., Pommier, Y. J. Biol. Chem. (2006) [Pubmed]
  5. Human Cytomegalovirus Disrupts both Ataxia Telangiectasia Mutated Protein (ATM)- and ATM-Rad3-Related Kinase-Mediated DNA Damage Responses during Lytic Infection. Luo, M.H., Rosenke, K., Czornak, K., Fortunato, E.A. J. Virol. (2007) [Pubmed]
  6. Deficiency of the Mre11 DNA repair complex in Alzheimer's disease brains. Jacobsen, E., Beach, T., Shen, Y., Li, R., Chang, Y. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  7. The DNA damage-dependent intra-S phase checkpoint is regulated by parallel pathways. Falck, J., Petrini, J.H., Williams, B.R., Lukas, J., Bartek, J. Nat. Genet. (2002) [Pubmed]
  8. The Mre11 complex is required for repair of hairpin-capped double-strand breaks and prevention of chromosome rearrangements. Lobachev, K.S., Gordenin, D.A., Resnick, M.A. Cell (2002) [Pubmed]
  9. An alternative mode of translation permits production of a variant NBS1 protein from the common Nijmegen breakage syndrome allele. Maser, R.S., Zinkel, R., Petrini, J.H. Nat. Genet. (2001) [Pubmed]
  10. Structural biochemistry and interaction architecture of the DNA double-strand break repair Mre11 nuclease and Rad50-ATPase. Hopfner, K.P., Karcher, A., Craig, L., Woo, T.T., Carney, J.P., Tainer, J.A. Cell (2001) [Pubmed]
  11. Inactivation of Mre11 does not affect VSG gene duplication mediated by homologous recombination in Trypanosoma brucei. Robinson, N.P., McCulloch, R., Conway, C., Browitt, A., Barry, J.D. J. Biol. Chem. (2002) [Pubmed]
  12. Translocation of MRE11 from the nucleus to the cytoplasm as a mechanism of radiosensitization by heat. Zhu, W.G., Seno, J.D., Beck, B.D., Dynlacht, J.R. Radiat. Res. (2001) [Pubmed]
  13. Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres. Zhu, X.D., Küster, B., Mann, M., Petrini, J.H., de Lange, T. Nat. Genet. (2000) [Pubmed]
  14. ATR-dependent phosphorylation and activation of ATM in response to UV treatment or replication fork stalling. Stiff, T., Walker, S.A., Cerosaletti, K., Goodarzi, A.A., Petermann, E., Concannon, P., O'driscoll, M., Jeggo, P.A. EMBO J. (2006) [Pubmed]
  15. Mre11 deficiency in Arabidopsis is associated with chromosomal instability in somatic cells and Spo11-dependent genome fragmentation during meiosis. Puizina, J., Siroky, J., Mokros, P., Schweizer, D., Riha, K. Plant Cell (2004) [Pubmed]
  16. Isolation of hMRE11B: failure to complement yeast mre11 defects due to species-specific protein interactions. Chamankhah, M., Wei, Y.F., Xiao, W. Gene (1998) [Pubmed]
  17. Mutations of an intronic repeat induce impaired MRE11 expression in primary human cancer with microsatellite instability. Giannini, G., Rinaldi, C., Ristori, E., Ambrosini, M.I., Cerignoli, F., Viel, A., Bidoli, E., Berni, S., D'Amati, G., Scambia, G., Frati, L., Screpanti, I., Gulino, A. Oncogene (2004) [Pubmed]
  18. Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis. Goedecke, W., Eijpe, M., Offenberg, H.H., van Aalderen, M., Heyting, C. Nat. Genet. (1999) [Pubmed]
  19. MRE11/RAD50 cleaves DNA in the AID/UNG-dependent pathway of immunoglobulin gene diversification. Larson, E.D., Cummings, W.J., Bednarski, D.W., Maizels, N. Mol. Cell (2005) [Pubmed]
  20. Replication protein A and the Mre11.Rad50.Nbs1 complex co-localize and interact at sites of stalled replication forks. Robison, J.G., Elliott, J., Dixon, K., Oakley, G.G. J. Biol. Chem. (2004) [Pubmed]
  21. DNA damage foci at dysfunctional telomeres. Takai, H., Smogorzewska, A., de Lange, T. Curr. Biol. (2003) [Pubmed]
  22. Neocarzinostatin induces Mre11 phosphorylation and focus formation through an ATM- and NBS1-dependent mechanism. Yuan, S.S., Chang, H.L., Hou, M.F., Chan, T.F., Kao, Y.H., Wu, Y.C., Su, J.H. Toxicology (2002) [Pubmed]
  23. Arsenic-induced Mre11 phosphorylation is cell cycle-dependent and defective in NBS cells. Yuan, S.S., Su, J.H., Hou, M.F., Yang, F.W., Zhao, S., Lee, E.Y. DNA Repair (Amst.) (2002) [Pubmed]
  24. Arginine methylation of MRE11 by PRMT1 is required for DNA damage checkpoint control. Boisvert, F.M., Déry, U., Masson, J.Y., Richard, S. Genes Dev. (2005) [Pubmed]
  25. The Mre11 complex is required for ATM activation and the G2/M checkpoint. Carson, C.T., Schwartz, R.A., Stracker, T.H., Lilley, C.E., Lee, D.V., Weitzman, M.D. EMBO J. (2003) [Pubmed]
  26. Linkage between Werner syndrome protein and the Mre11 complex via Nbs1. Cheng, W.H., von Kobbe, C., Opresko, P.L., Arthur, L.M., Komatsu, K., Seidman, M.M., Carney, J.P., Bohr, V.A. J. Biol. Chem. (2004) [Pubmed]
  27. NBS1 localizes to gamma-H2AX foci through interaction with the FHA/BRCT domain. Kobayashi, J., Tauchi, H., Sakamoto, S., Nakamura, A., Morishima, K., Matsuura, S., Kobayashi, T., Tamai, K., Tanimoto, K., Komatsu, K. Curr. Biol. (2002) [Pubmed]
  28. Werner syndrome protein, the MRE11 complex and ATR: menage-à-trois in guarding genome stability during DNA replication? Pichierri, P., Franchitto, A. Bioessays (2004) [Pubmed]
  29. Protein kinase CK2 interacts with Chk2 and phosphorylates Mre11 on serine 649. Kim, S.T. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  30. MDC1 is required for the intra-S-phase DNA damage checkpoint. Goldberg, M., Stucki, M., Falck, J., D'Amours, D., Rahman, D., Pappin, D., Bartek, J., Jackson, S.P. Nature (2003) [Pubmed]
  31. The Nijmegen breakage syndrome protein is essential for Mre11 phosphorylation upon DNA damage. Dong, Z., Zhong, Q., Chen, P.L. J. Biol. Chem. (1999) [Pubmed]
  32. MRE11/RAD50/NBS1: complex activities. Assenmacher, N., Hopfner, K.P. Chromosoma (2004) [Pubmed]
  33. DNA replication arrest in XP variant cells after UV exposure is diverted into an Mre11-dependent recombination pathway by the kinase inhibitor wortmannin. Limoli, C.L., Laposa, R., Cleaver, J.E. Mutat. Res. (2002) [Pubmed]
  34. ATM and ATR promote Mre11 dependent restart of collapsed replication forks and prevent accumulation of DNA breaks. Trenz, K., Smith, E., Smith, S., Costanzo, V. EMBO J. (2006) [Pubmed]
  35. MRE11 mutations and impaired ATM-dependent responses in an Italian family with ataxia-telangiectasia-like disorder. Delia, D., Piane, M., Buscemi, G., Savio, C., Palmeri, S., Lulli, P., Carlessi, L., Fontanella, E., Chessa, L. Hum. Mol. Genet. (2004) [Pubmed]
  36. MRE11 expression is impaired in gastric cancer with microsatellite instability. Ottini, L., Falchetti, M., Saieva, C., De Marco, M., Masala, G., Zanna, I., Paglierani, M., Giannini, G., Gulino, A., Nesi, G., Mariani Costantini, R., Palli, D. Carcinogenesis (2004) [Pubmed]
  37. The Haemophilus ducreyi cytolethal distending toxin activates sensors of DNA damage and repair complexes in proliferating and non-proliferating cells. Li, L., Sharipo, A., Chaves-Olarte, E., Masucci, M.G., Levitsky, V., Thelestam, M., Frisan, T. Cell. Microbiol. (2002) [Pubmed]
  38. Radiosensitization of heat resistant human tumour cells by 1 hour at 41.1 degrees C and its effect on DNA repair. Xu, M., Myerson, R.J., Straube, W.L., Moros, E.G., Lagroye, I., Wang, L.L., Lee, J.T., Roti Roti, J.L. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. (2002) [Pubmed]
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