Mre11a

Summary

Gene Symbol: Mre11a
Description: MRE11A homolog A, double strand break repair nuclease
Alias: Mre11, Mre11b, double-strand break repair protein MRE11, double-strand break repair protein MRE11A, MRE11 homolog 1, MRE11 homolog A, meiotic recombination 11 homolog 1, meiotic recombination 11 homolog A, mmMRE11A
Species: mouse
Products:     Mre11a

Top Publications

  1. Theunissen J, Kaplan M, Hunt P, Williams B, Ferguson D, Alt F, et al. Checkpoint failure and chromosomal instability without lymphomagenesis in Mre11(ATLD1/ATLD1) mice. Mol Cell. 2003;12:1511-23 pubmed
    In this study, mice expressing one of the two Mre11 alleles inherited in the human ataxia-telangiectasia like disorder (A-TLD) were derived...
  2. Cherry S, Adelman C, Theunissen J, Hassold T, Hunt P, Petrini J. The Mre11 complex influences DNA repair, synapsis, and crossing over in murine meiosis. Curr Biol. 2007;17:373-8 pubmed
    The Mre11 complex (consisting of MRE11, RAD50, and NBS1/Xrs2) is required for double-strand break (DSB) formation, processing, and checkpoint signaling during meiotic cell division in S. cerevisiae...
  3. Stracker T, Morales M, Couto S, Hussein H, Petrini J. The carboxy terminus of NBS1 is required for induction of apoptosis by the MRE11 complex. Nature. 2007;447:218-21 pubmed
    The MRE11 complex (MRE11, RAD50 and NBS1) and the ataxia-telangiectasia mutated (ATM) kinase function in the same DNA damage response pathway to effect cell cycle checkpoint activation and apoptosis...
  4. Xiao Y, Weaver D. Conditional gene targeted deletion by Cre recombinase demonstrates the requirement for the double-strand break repair Mre11 protein in murine embryonic stem cells. Nucleic Acids Res. 1997;25:2985-91 pubmed
    ..The MRE11 gene has previously been implicated in DSB repair in the yeast Saccharomyces cerevisiae ...
  5. Buis J, Wu Y, Deng Y, Leddon J, Westfield G, Eckersdorff M, et al. Mre11 nuclease activity has essential roles in DNA repair and genomic stability distinct from ATM activation. Cell. 2008;135:85-96 pubmed publisher
    The Mre11/Rad50/NBS1 (MRN) complex maintains genomic stability by bridging DNA ends and initiating DNA damage signaling through activation of the ATM kinase...
  6. Helmink B, Bredemeyer A, Lee B, Huang C, Sharma G, Walker L, et al. MRN complex function in the repair of chromosomal Rag-mediated DNA double-strand breaks. J Exp Med. 2009;206:669-79 pubmed publisher
    The Mre11-Rad50-Nbs1 (MRN) complex functions in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) at postreplicative stages of the cell cycle...
  7. Shull E, Lee Y, Nakane H, Stracker T, Zhao J, Russell H, et al. Differential DNA damage signaling accounts for distinct neural apoptotic responses in ATLD and NBS. Genes Dev. 2009;23:171-80 pubmed publisher
    The MRN complex (Mre11/RAD50/NBS1) and ATM (ataxia telangiectasia, mutated) are critical for the cellular response to DNA damage...
  8. Morales A, Carrero J, Hung P, Tubbs A, Andrews J, Edelson B, et al. A type I IFN-dependent DNA damage response regulates the genetic program and inflammasome activation in macrophages. elife. 2017;6: pubmed publisher
    ..Thus, genomic DNA DSBs act as signaling intermediates in murine macrophages, regulating innate immune responses through the initiation of a type I IFN-dependent DDR. ..
  9. Kim G, Georg I, Scherthan H, Merkenschlager M, Guillou F, Scherer G, et al. Dicer is required for Sertoli cell function and survival. Int J Dev Biol. 2010;54:867-75 pubmed publisher
    ..Taken together, the results of this study show that Dicer is required for Sertoli cell function and survival and for spermatogenesis in mice. ..

More Information

Publications45

  1. Attwooll C, Akpinar M, Petrini J. The mre11 complex and the response to dysfunctional telomeres. Mol Cell Biol. 2009;29:5540-51 pubmed publisher
    In this study, we examine the telomeric functions of the mammalian Mre11 complex by using hypomorphic Mre11 and Nbs1 mutants (Mre11(ATLD1/ATLD1) and Nbs1(Delta)(B/)(DeltaB), respectively)...
  2. Dimitrova N, de Lange T. Cell cycle-dependent role of MRN at dysfunctional telomeres: ATM signaling-dependent induction of nonhomologous end joining (NHEJ) in G1 and resection-mediated inhibition of NHEJ in G2. Mol Cell Biol. 2009;29:5552-63 pubmed publisher
    Here, we address the role of the MRN (Mre11/Rad50/Nbs1) complex in the response to telomeres rendered dysfunctional by deletion of the shelterin component TRF2...
  3. Spehalski E, Capper K, Smith C, Morgan M, Dinkelmann M, Buis J, et al. MRE11 Promotes Tumorigenesis by Facilitating Resistance to Oncogene-Induced Replication Stress. Cancer Res. 2017;77:5327-5338 pubmed publisher
    Hypomorphic mutations in the genes encoding the MRE11/RAD50/NBS1 (MRN) DNA repair complex lead to cancer-prone syndromes...
  4. Pacheco S, Marcet Ortega M, Lange J, Jasin M, Keeney S, Roig I. The ATM signaling cascade promotes recombination-dependent pachytene arrest in mouse spermatocytes. PLoS Genet. 2015;11:e1005017 pubmed publisher
    ..spermatocytes also progress to an H1t-positive stage if ATM activity is attenuated by hypomorphic mutations in Mre11 or Nbs1 or by elimination of the ATM-effector kinase CHK2...
  5. Katyal S, Lee Y, Nitiss K, Downing S, Li Y, Shimada M, et al. Aberrant topoisomerase-1 DNA lesions are pathogenic in neurodegenerative genome instability syndromes. Nat Neurosci. 2014;17:813-21 pubmed publisher
    ..Our results identify a critical endogenous pathogenic lesion associated with neurodegenerative syndromes arising from DNA repair deficiency, indicating that genome integrity is important for preventing disease in the nervous system. ..
  6. Regal J, Festerling T, Buis J, Ferguson D. Disease-associated MRE11 mutants impact ATM/ATR DNA damage signaling by distinct mechanisms. Hum Mol Genet. 2013;22:5146-59 pubmed publisher
    ..Here, we have examined the impact on DNA damage signaling of several disease-associated MRE11A alleles to gain greater understanding of the mechanisms underlying the diverse disease sequelae of ATLD...
  7. Rotolo J, Mesicek J, Maj J, Truman J, Haimovitz Friedman A, Kolesnick R, et al. Regulation of ceramide synthase-mediated crypt epithelium apoptosis by DNA damage repair enzymes. Cancer Res. 2010;70:957-67 pubmed publisher
    ..was mitigated in irradiated gain-of-function Rad50(s/s) mice, and epistasis studies order Rad50 upstream of Mre11. These studies suggest unrepaired DNA DSBs as causative in target reordering in intestinal SCCs...
  8. Stracker T, Williams B, Deriano L, Theunissen J, Adelman C, Roth D, et al. Artemis and nonhomologous end joining-independent influence of DNA-dependent protein kinase catalytic subunit on chromosome stability. Mol Cell Biol. 2009;29:503-14 pubmed publisher
    ..Similar to the loss of ATM, hypomorphic mutations of Mre11 (Mre11(ATLD1)) led to synthetic lethality when juxtaposed with DNA-PKcs deficiency (Prkdc(scid))...
  9. Spycher C, Miller E, Townsend K, Pavic L, Morrice N, Janscak P, et al. Constitutive phosphorylation of MDC1 physically links the MRE11-RAD50-NBS1 complex to damaged chromatin. J Cell Biol. 2008;181:227-40 pubmed publisher
    The MRE11-RAD50-Nijmegen breakage syndrome 1 (NBS1 [MRN]) complex accumulates at sites of DNA double-strand breaks (DSBs) in microscopically discernible nuclear foci...
  10. Morales M, Theunissen J, Kim C, Kitagawa R, Kastan M, Petrini J. The Rad50S allele promotes ATM-dependent DNA damage responses and suppresses ATM deficiency: implications for the Mre11 complex as a DNA damage sensor. Genes Dev. 2005;19:3043-54 pubmed
    Genetic and cytologic data from Saccharomyces cerevisiae and mammals implicate the Mre11 complex, consisting of Mre11, Rad50, and Nbs1, as a sensor of DNA damage, and indicate that the complex influences the activity of ataxia-..
  11. Dmitrieva N, Bulavin D, Burg M. High NaCl causes Mre11 to leave the nucleus, disrupting DNA damage signaling and repair. Am J Physiol Renal Physiol. 2003;285:F266-74 pubmed
    ..In this study, we describe a novel mechanism that contributes to this genotoxicity. The Mre11 exonuclease complex is a central component of DNA damage response...
  12. Gong Y, Handa N, Kowalczykowski S, de Lange T. PHF11 promotes DSB resection, ATR signaling, and HR. Genes Dev. 2017;31:46-58 pubmed publisher
    ..These findings reveal a role for PHF11 in DSB resection, DNA damage signaling, and DSB repair. ..
  13. Stracker T, Couto S, Cordon Cardo C, Matos T, Petrini J. Chk2 suppresses the oncogenic potential of DNA replication-associated DNA damage. Mol Cell. 2008;31:21-32 pubmed publisher
    The Mre11 complex (Mre11, Rad50, and Nbs1) and Chk2 have been implicated in the DNA-damage response, an inducible process required for the suppression of malignancy...
  14. Yuan J, Chen J. MRE11-RAD50-NBS1 complex dictates DNA repair independent of H2AX. J Biol Chem. 2010;285:1097-104 pubmed publisher
    ..We demonstrate that the MRE11-RAD50-NBS1 (MRN) complex acts to promote DNA end resection and the generation of single-stranded DNA, which is ..
  15. Yanagihara H, Kobayashi J, Tateishi S, Kato A, Matsuura S, Tauchi H, et al. NBS1 recruits RAD18 via a RAD6-like domain and regulates Pol ?-dependent translesion DNA synthesis. Mol Cell. 2011;43:788-97 pubmed publisher
    ..Thus, in addition to chromosomal break repair, NBS1 plays a key role in translesion DNA synthesis. ..
  16. Bender C, Sikes M, Sullivan R, Huye L, Le Beau M, Roth D, et al. Cancer predisposition and hematopoietic failure in Rad50(S/S) mice. Genes Dev. 2002;16:2237-51 pubmed
    b>Mre11, Rad50, and Nbs1 function in a protein complex that is central to the metabolism of chromosome breaks. Null mutants of each are inviable...
  17. Barrionuevo F, Georg I, Scherthan H, Lecureuil C, Guillou F, Wegner M, et al. Testis cord differentiation after the sex determination stage is independent of Sox9 but fails in the combined absence of Sox9 and Sox8. Dev Biol. 2009;327:301-12 pubmed publisher
    ..This study shows that testis cord differentiation is independent of Sox9, and that concerted Sox9 and Sox8 function in post E14.0 Sertoli cells is essential for the maintenance of testicular function. ..
  18. Kim J, Grosbart M, Anand R, Wyman C, Cejka P, Petrini J. The Mre11-Nbs1 Interface Is Essential for Viability and Tumor Suppression. Cell Rep. 2017;18:496-507 pubmed publisher
    The Mre11 complex (Mre11, Rad50, and Nbs1) is integral to both DNA repair and ataxia telangiectasia mutated (ATM)-dependent DNA damage signaling...
  19. Mayer A, Baran V, Sakakibara Y, Brzakova A, Ferencova I, Motlik J, et al. DNA damage response during mouse oocyte maturation. Cell Cycle. 2016;15:546-58 pubmed publisher
    ..b>MRE11, but not ATM, is essential to detect DSBs in prophase I and is involved in H2AX phosphorylation during metaphase I...
  20. Hartlerode A, Morgan M, Wu Y, Buis J, Ferguson D. Recruitment and activation of the ATM kinase in the absence of DNA-damage sensors. Nat Struct Mol Biol. 2015;22:736-43 pubmed publisher
    ..Using mouse cells containing targeted mutant alleles of Mre11 (Mre11a) and/or Ku70 (Xrcc6), together with pharmacologic kinase inhibition, we demonstrate that ATM can be activated by ..
  21. Franchitto A, Pichierri P, Piergentili R, Crescenzi M, Bignami M, Palitti F. The mammalian mismatch repair protein MSH2 is required for correct MRE11 and RAD51 relocalization and for efficient cell cycle arrest induced by ionizing radiation in G2 phase. Oncogene. 2003;22:2110-20 pubmed
    ..Cell survival, checkpoint functions and relocalization of the recombination-related proteins MRE11 and RAD51 were analysed in embryonic fibroblasts derived from MSH2(+/+) and MSH2(-/-) mice, and in MSH2-proficient ..
  22. Sengupta S, Robles A, Linke S, Sinogeeva N, Zhang R, Pedeux R, et al. Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest. J Cell Biol. 2004;166:801-13 pubmed
    ..Once the ATR/Chk1- and 53BP1-mediated signal from replicational stress is received, BLM functions in multiple downstream repair processes, thereby fulfilling its role as a caretaker tumor suppressor. ..
  23. Gupta G, Vanness K, Barlas A, Manova Todorova K, Wen Y, Petrini J. The Mre11 complex suppresses oncogene-driven breast tumorigenesis and metastasis. Mol Cell. 2013;52:353-65 pubmed publisher
    ..breast tumorigenesis in a series of mutant mouse strains with specific DDR deficiencies to reveal a role for the Mre11 complex in the response to oncogene activation...
  24. Chang F, McGhie J, Chan F, Tang M, Anderson M, Mann J, et al. PML bodies provide an important platform for the maintenance of telomeric chromatin integrity in embryonic stem cells. Nucleic Acids Res. 2013;41:4447-58 pubmed publisher
    ..Our study demonstrates that PML bodies act as epigenetic regulators by serving as platforms for the assembly of the telomeric chromatin to ensure a faithful inheritance of epigenetic information at the telomere. ..
  25. Dinkelmann M, Spehalski E, Stoneham T, Buis J, Wu Y, Sekiguchi J, et al. Multiple functions of MRN in end-joining pathways during isotype class switching. Nat Struct Mol Biol. 2009;16:808-13 pubmed publisher
    The Mre11-Rad50-NBS1 (MRN) complex has many roles in response to DNA double-strand breaks, but its functions in repair by nonhomologous end joining (NHEJ) pathways are poorly understood...
  26. Alt J, Bouska A, Fernandez M, Cerny R, Xiao H, Eischen C. Mdm2 binds to Nbs1 at sites of DNA damage and regulates double strand break repair. J Biol Chem. 2005;280:18771-81 pubmed
    ..Here we report the identification of a specific association of Mdm2 with Mre11, Nbs1, and Rad50, a DNA double strand break repair complex...
  27. Kondo T, Kobayashi J, Saitoh T, Maruyama K, Ishii K, Barber G, et al. DNA damage sensor MRE11 recognizes cytosolic double-stranded DNA and induces type I interferon by regulating STING trafficking. Proc Natl Acad Sci U S A. 2013;110:2969-74 pubmed publisher
    ..Here we show that the DNA damage sensor, meiotic recombination 11 homolog A (MRE11), serves as a cytosolic sensor for dsDNA...
  28. Yu Z, Vogel G, Coulombe Y, Dubeau D, Spehalski E, Hébert J, et al. The MRE11 GAR motif regulates DNA double-strand break processing and ATR activation. Cell Res. 2012;22:305-20 pubmed publisher
    The MRE11/RAD50/NBS1 complex is the primary sensor rapidly recruited to DNA double-strand breaks (DSBs). MRE11 is known to be arginine methylated by PRMT1 within its glycine-arginine-rich (GAR) motif...
  29. Inagaki A, Roset R, Petrini J. Functions of the MRE11 complex in the development and maintenance of oocytes. Chromosoma. 2016;125:151-62 pubmed publisher
    The MRE11 complex (MRE11, RAD50, and NBS1) is a central component of the DNA damage response, governing both double-strand break repair and DNA damage response signaling...
  30. Kanakkanthara A, Jeganathan K, Limzerwala J, Baker D, Hamada M, Nam H, et al. Cyclin A2 is an RNA binding protein that controls Mre11 mRNA translation. Science. 2016;353:1549-1552 pubmed
    ..Underlying the chromosomal instability is a failure to up-regulate the meiotic recombination 11 (Mre11) nuclease in S phase, which leads to impaired resolution of stalled replication forks, insufficient repair of ..
  31. Vissinga C, Yeo T, Warren S, Brawley J, Phillips J, Cerosaletti K, et al. Nuclear export of NBN is required for normal cellular responses to radiation. Mol Cell Biol. 2009;29:1000-6 pubmed publisher
    Nijmegen breakage syndrome arises from hypomorphic mutations in the NBN gene encoding nibrin, a component of the MRE11/RAD50/nibrin (MRN) complex...
  32. Bördlein A, Scherthan H, Nelkenbrecher C, Molter T, Bösl M, Dippold C, et al. SPOC1 (PHF13) is required for spermatogonial stem cell differentiation and sustained spermatogenesis. J Cell Sci. 2011;124:3137-48 pubmed publisher
    ..Taken together, the data argue that SPOC1 is indispensable for stem cell differentiation in the testis and for sustained spermatogenesis. ..
  33. Dmitrieva N, Malide D, Burg M. Mre11 is expressed in mammalian mitochondria where it binds to mitochondrial DNA. Am J Physiol Regul Integr Comp Physiol. 2011;301:R632-40 pubmed publisher
    b>Mre11 is a critical participant in upkeep of nuclear DNA, its repair, replication, meiosis, and maintenance of telomeres. The upkeep of mitochondrial DNA (mtDNA) is less well characterized, and whether Mre11 participates has been unknown...
  34. Morales M, Liu Y, Laiakis E, Morgan W, Nimer S, Petrini J. DNA damage signaling in hematopoietic cells: a role for Mre11 complex repair of topoisomerase lesions. Cancer Res. 2008;68:2186-93 pubmed publisher
    The Mre11 complex promotes DNA double-strand break repair and regulates DNA damage signaling via activation of the ataxia-telangiectasia mutated (ATM) kinase...
  35. Xie A, Kwok A, Scully R. Role of mammalian Mre11 in classical and alternative nonhomologous end joining. Nat Struct Mol Biol. 2009;16:814-8 pubmed publisher
    The mammalian Mre11-Rad50-Nbs1 (MRN) complex coordinates double-strand break signaling with repair by homologous recombination and is associated with the H2A...
  36. Deng Y, Guo X, Ferguson D, Chang S. Multiple roles for MRE11 at uncapped telomeres. Nature. 2009;460:914-8 pubmed publisher
    ..The mammalian MRE11-RAD50-NBS1 (MRN; NBS1 is also known as NBN) complex interacts with ATM to sense chromosomal double-strand breaks ..