EME1

Summary

Gene Symbol: EME1
Description: essential meiotic structure-specific endonuclease 1
Alias: MMS4L, SLX2A, crossover junction endonuclease EME1, MMS4 homolog, SLX2 structure-specific endonuclease subunit homolog A, essential meiotic endonuclease 1 homolog 1, essential meiotic endonuclease 1 homolog 2, hMMS4, homolog of yeast EME1 endonuclease
Species: human
Products:     EME1

Top Publications

  1. Blais V, Gao H, Elwell C, Boddy M, Gaillard P, Russell P, et al. RNA interference inhibition of Mus81 reduces mitotic recombination in human cells. Mol Biol Cell. 2004;15:552-62 pubmed
    ..In yeast Mus81 associates with a second subunit, Eme1 or Mms4, which is essential for endonuclease activity in vitro and for in vivo function...
  2. Oğrünç M, Sancar A. Identification and characterization of human MUS81-MMS4 structure-specific endonuclease. J Biol Chem. 2003;278:21715-20 pubmed
    ..Here, we report identification of the binding partner of human MUS81, which we designate hMMS4. Using immunoaffinity purification we show that hMUS81 or hMMS4 alone have no detectable nuclease activity, but ..
  3. Hiyama T, Katsura M, Yoshihara T, Ishida M, Kinomura A, Tonda T, et al. Haploinsufficiency of the Mus81-Eme1 endonuclease activates the intra-S-phase and G2/M checkpoints and promotes rereplication in human cells. Nucleic Acids Res. 2006;34:880-92 pubmed
    The Mus81-Eme1 complex is a structure-specific endonuclease that preferentially cleaves nicked Holliday junctions, 3'-flap structures and aberrant replication fork structures...
  4. Wyatt H, Sarbajna S, Matos J, West S. Coordinated actions of SLX1-SLX4 and MUS81-EME1 for Holliday junction resolution in human cells. Mol Cell. 2013;52:234-47 pubmed publisher
    ..Here, we show that three structure-selective endonucleases, namely SLX1-SLX4, MUS81-EME1, and GEN1, define two pathways of HJ resolution in human cells...
  5. Munoz I, Hain K, Déclais A, Gardiner M, Toh G, Sanchez Pulido L, et al. Coordination of structure-specific nucleases by human SLX4/BTBD12 is required for DNA repair. Mol Cell. 2009;35:116-27 pubmed publisher
    ..Here we describe the identification of human SLX4, a scaffold for DNA repair nucleases XPF-ERCC1, MUS81-EME1, and SLX1...
  6. Mazina O, Mazin A. Human Rad54 protein stimulates human Mus81-Eme1 endonuclease. Proc Natl Acad Sci U S A. 2008;105:18249-54 pubmed publisher
    ..a key protein of homologous recombination, physically interacts with a DNA structure-specific endonuclease, Mus81-Eme1. Genetic data indicate that Mus81-Eme1 and Rad54 might function together in the repair of damaged DNA...
  7. Ciccia A, Constantinou A, West S. Identification and characterization of the human mus81-eme1 endonuclease. J Biol Chem. 2003;278:25172-8 pubmed
    ..In fission yeast, the Mus81-Eme1 endonuclease complex (Mus81-Mms4 in Saccharomyces cerevisiae) has been implicated in the processing of aberrant ..
  8. Abraham J, Lemmers B, Hande M, Moynahan M, Chahwan C, Ciccia A, et al. Eme1 is involved in DNA damage processing and maintenance of genomic stability in mammalian cells. EMBO J. 2003;22:6137-47 pubmed
    Yeast and human Eme1 protein, in complex with Mus81, constitute an endonuclease that cleaves branched DNA structures, especially those arising during stalled DNA replication...
  9. Taylor E, McGowan C. Cleavage mechanism of human Mus81-Eme1 acting on Holliday-junction structures. Proc Natl Acad Sci U S A. 2008;105:3757-62 pubmed publisher
    ..The human Mus81-Eme1 endonuclease is involved in recombination repair, but the exact structures it acts on in vivo are not known...

More Information

Publications57

  1. Fekairi S, Scaglione S, Chahwan C, Taylor E, Tissier A, Coulon S, et al. Human SLX4 is a Holliday junction resolvase subunit that binds multiple DNA repair/recombination endonucleases. Cell. 2009;138:78-89 pubmed publisher
    ..Furthermore, we show that SLX4 binds the XPF(ERCC4) and MUS81 subunits of the XPF-ERCC1 and MUS81-EME1 endonucleases and is required for DNA interstrand crosslink repair...
  2. Zhou R, Yang O, Déclais A, Jin H, Gwon G, Freeman A, et al. Junction resolving enzymes use multivalency to keep the Holliday junction dynamic. Nat Chem Biol. 2019;15:269-275 pubmed publisher
    ..of resolving enzymes from bacteriophages (T7 endonuclease I), bacteria (RuvC), fungi (GEN1) and humans (hMus81-Eme1) showed that both types of HJ dynamics still occur after enzyme binding...
  3. Noguchi E, Noguchi C, McDonald W, Yates J, Russell P. Swi1 and Swi3 are components of a replication fork protection complex in fission yeast. Mol Cell Biol. 2004;24:8342-55 pubmed
    ..correlated with the Rad22-dependent appearance of Holliday junction (HJ)-like structures in cells lacking Mus81-Eme1 HJ resolvase...
  4. Wechsler T, Newman S, West S. Aberrant chromosome morphology in human cells defective for Holliday junction resolution. Nature. 2011;471:642-6 pubmed publisher
    ..MUS81-EME1 (refs 4-7), SLX1-SLX4 (refs 8-11) and GEN1 (refs 12, 13) also process Holliday junctions but, in contrast to the ..
  5. MacGregor T, Carter R, Gillies R, Findlay J, Kartsonaki C, Castro Giner F, et al. Translational study identifies XPF and MUS81 as predictive biomarkers for oxaliplatin-based peri-operative chemotherapy in patients with esophageal adenocarcinoma. Sci Rep. 2018;8:7265 pubmed publisher
    ..05). From clinical associations with outcomes, two genes, ERCC1 and EME1, were identified as candidate biomarkers...
  6. Oke A, Anderson C, Yam P, Fung J. Controlling meiotic recombinational repair - specifying the roles of ZMMs, Sgs1 and Mus81/Mms4 in crossover formation. PLoS Genet. 2014;10:e1004690 pubmed publisher
    ..Our analysis suggests that Mus81/Mms4 (Eme1), rather than just being a minor resolvase for COs is crucial for both COs and NCOs in preventing chromosome ..
  7. García Luis J, Machín F. Mus81-Mms4 and Yen1 resolve a novel anaphase bridge formed by noncanonical Holliday junctions. Nat Commun. 2014;5:5652 pubmed publisher
    ..Here we report that the overlapping actions of the structure-selective endonucleases (SSEs) Mus81-Mms4/EME1 and Yen1/GEN1, but not Slx1-Slx4, are also essential to prevent the formation of spontaneous SCBs that depend on ..
  8. Sanyal S, Molnarova L, Richterova J, Huraiová B, Benko Z, Polakova S, et al. Mutations that prevent methylation of cohesin render sensitivity to DNA damage in S. pombe. J Cell Sci. 2018;131: pubmed publisher
    ..to DNA-damaging agents and show positive genetic interactions with mutations in genes encoding the Mus81-Eme1 endonuclease...
  9. Lorenz A, Mehats A, Osman F, Whitby M. Rad51/Dmc1 paralogs and mediators oppose DNA helicases to limit hybrid DNA formation and promote crossovers during meiotic recombination. Nucleic Acids Res. 2014;42:13723-35 pubmed publisher
    ..DNA helicase/translocase Fml1 and the RecQ-type DNA helicase Rqh1 to limit hybrid DNA formation and promote Mus81-Eme1-dependent COs...
  10. Xia J, Chen L, Mei Q, Ma C, Halliday J, Lin H, et al. Holliday junction trap shows how cells use recombination and a junction-guardian role of RecQ helicase. Sci Adv. 2016;2:e1601605 pubmed publisher
    ..i>RAD51 and find that cancer genome expression data implicate the orthologs BLM and RECQL4 in conjunction with EME1 and GEN1 as probable HJ reducers in such cancers. Our results support RecA-overproducing E...
  11. Arter M, Hurtado Nieves V, Oke A, Zhuge T, Wettstein R, Fung J, et al. Regulated Crossing-Over Requires Inactivation of Yen1/GEN1 Resolvase during Meiotic Prophase I. Dev Cell. 2018;45:785-800.e6 pubmed publisher
    ..Thus, active suppression of Yen1 function, and by inference also of Mus81-Mms4(EME1) and Slx1-Slx4(BTBD12) resolvases, avoids precocious resolution of recombination intermediates to enable meiotic ..
  12. Palma A, Pugliese G, Murfuni I, Marabitti V, Malacaria E, Rinalducci S, et al. Phosphorylation by CK2 regulates MUS81/EME1 in mitosis and after replication stress. Nucleic Acids Res. 2018;46:5109-5124 pubmed publisher
    ..phosphorylation at Serine 87 is suppressed in S-phase and is mainly detected in the MUS81 molecules associated with EME1. Loss of CK2-dependent MUS81 phosphorylation contributes modestly to chromosome integrity, however, expression of ..
  13. Minocherhomji S, Ying S, Bjerregaard V, Bursomanno S, Aleliunaite A, Wu W, et al. Replication stress activates DNA repair synthesis in mitosis. Nature. 2015;528:286-90 pubmed publisher
    ..The MUS81-EME1 structure-specific endonuclease promotes the appearance of chromosome gaps or breaks at CFSs following replicative ..
  14. Wang X, Wang H, Guo B, Zhang Y, Gong Y, Zhang C, et al. Gen1 and Eme1 Play Redundant Roles in DNA Repair and Meiotic Recombination in Mice. DNA Cell Biol. 2016;35:585-590 pubmed
    ..cultured mammalian cells, such redundancy also exists between Yen1 ortholog GEN1 and the Mus81-Mms1 ortholog MUS81-EME1. In this report, we further tested if GEN1 and EME1 redundantly affect HJ-related physiological processes in mice...
  15. Di Marco S, Hasanova Z, Kanagaraj R, Chappidi N, Altmannova V, Menon S, et al. RECQ5 Helicase Cooperates with MUS81 Endonuclease in Processing Stalled Replication Forks at Common Fragile Sites during Mitosis. Mol Cell. 2017;66:658-671.e8 pubmed publisher
    The MUS81-EME1 endonuclease cleaves late replication intermediates at common fragile sites (CFSs) during early mitosis to trigger DNA-repair synthesis that ensures faithful chromosome segregation...
  16. Wyatt H, Laister R, Martin S, Arrowsmith C, West S. The SMX DNA Repair Tri-nuclease. Mol Cell. 2017;65:848-860.e11 pubmed publisher
    ..Resolution of these potentially toxic structures requires the MUS81-EME1 endonuclease, which is activated at prometaphase by formation of the SMX tri-nuclease containing three DNA repair ..
  17. Bhowmick R, Minocherhomji S, Hickson I. RAD52 Facilitates Mitotic DNA Synthesis Following Replication Stress. Mol Cell. 2016;64:1117-1126 pubmed publisher
    ..This mitotic DNA synthesis, termed MiDAS, requires the MUS81-EME1 endonuclease and a non-catalytic subunit of the Pol-delta complex, POLD3...
  18. Nowotny M, Gaur V. Structure and mechanism of nucleases regulated by SLX4. Curr Opin Struct Biol. 2016;36:97-105 pubmed publisher
    ..Among these proteins are three structure-selective nucleases (SSEs). XPF-ERCC1 and MUS81-EME1 are structurally similar and function as heterodimers of highly similar subunits, in which only one is active...
  19. West S, Blanco M, Chan Y, Matos J, Sarbajna S, Wyatt H. Resolution of Recombination Intermediates: Mechanisms and Regulation. Cold Spring Harb Symp Quant Biol. 2015;80:103-9 pubmed publisher
    ..These involve (1) BLM-Topoisomerase III?-RMI1-RMI2 (BTR complex), (2) SLX1-SLX4-MUS81-EME1 (SLX-MUS complex), and (3) GEN1...
  20. Xiao Z, Chang J, Hendriks I, Sigurðsson J, Olsen J, Vertegaal A. System-wide Analysis of SUMOylation Dynamics in Response to Replication Stress Reveals Novel Small Ubiquitin-like Modified Target Proteins and Acceptor Lysines Relevant for Genome Stability. Mol Cell Proteomics. 2015;14:1419-34 pubmed publisher
    ..ATR-interacting protein ATRIP, the Bloom syndrome protein and the BLM-binding partner RMI1, the crossover junction endonuclease EME1, BRCA1, and CHAF1A...
  21. Wang C, Higgins J, He Y, Lu P, Zhang D, Liang W. Resolvase OsGEN1 Mediates DNA Repair by Homologous Recombination. Plant Physiol. 2017;173:1316-1329 pubmed publisher
    ..In eukaryotes, such as budding yeast, mice, worms, and humans, Yen1/GEN1 work together with Mus81-Mms4/MUS81-EME1 and Slx1-Slx4/SLX1-SLX4 in DNA repair by homologous recombination to maintain genome stability...
  22. Carter R, Westhorpe A, Romero M, Habtemariam A, Gallevo C, Bark Y, et al. Radiosensitisation of human colorectal cancer cells by ruthenium(II) arene anticancer complexes. Sci Rep. 2016;6:20596 pubmed publisher
    ..Colorectal cancer cells deficient in DNA damage repair proteins, EME1 and MUS81, were significantly more sensitive to both agents...
  23. Osman F, Gaskell L, Whitby M. Efficient second strand cleavage during Holliday junction resolution by RuvC requires both increased junction flexibility and an exposed 5' phosphate. PLoS ONE. 2009;4:e5347 pubmed publisher
    ..superfamily called RuvC, whereas in Schizosaccharomyces pombe it has been attributed to the XPF family member Mus81-Eme1. HJ resolution is achieved through the sequential cleavage of two strands of like polarity at or close to the ..
  24. Véquaud E, Desplanques G, Jézéquel P, Juin P, Barillé Nion S. Survivin contributes to DNA repair by homologous recombination in breast cancer cells. Breast Cancer Res Treat. 2016;155:53-63 pubmed publisher
    ..of a set of genes involved in HR, decreases RAD51 protein expression and impairs the endonuclease complex MUS81/EME1 involved in the resolution of Holliday junctions...
  25. Sánchez A, Russell P. Ku stabilizes replication forks in the absence of Brc1. PLoS ONE. 2015;10:e0126598 pubmed publisher
    ..In brc1∆ pku80∆ cells, nuclear foci of Rad52 homologous recombination (HR) protein increase and Mus81-Eme1 Holliday junction resolvase becomes critical, indicating increased replication fork instability...
  26. Chang J, Yeh R, Wiencke J, Wiemels J, Smirnov I, Pico A, et al. Pathway analysis of single-nucleotide polymorphisms potentially associated with glioblastoma multiforme susceptibility using random forests. Cancer Epidemiol Biomarkers Prev. 2008;17:1368-73 pubmed publisher
    ..5% and P = 0.09. Three SNPs (rs1047840 of EXO1, rs12450550 of EME1, and rs799917 of BRCA1) of the DNA repair pathway were identified as promising candidates for further replication...
  27. Saugar I, Jiménez Martín A, Tercero J. Subnuclear Relocalization of Structure-Specific Endonucleases in Response to DNA Damage. Cell Rep. 2017;20:1553-1562 pubmed publisher
    ..Here, we show that the structure-specific endonuclease Mus81-Mms4/EME1 relocalizes to subnuclear foci following DNA damage and colocalizes with the endonucleases Rad1-Rad10 (XPF-ERCC1) ..
  28. Tian Y, Paramasivam M, Ghosal G, Chen D, Shen X, Huang Y, et al. UHRF1 contributes to DNA damage repair as a lesion recognition factor and nuclease scaffold. Cell Rep. 2015;10:1957-66 pubmed publisher
    ..These results suggest that UHRF1 promotes recruitment of lesion-processing activities via its affinity to recognize DNA damage and functions as a nuclease recruitment scaffold in parallel to the FA pathway. ..
  29. Blondot M, Dragin L, Lahouassa H, Margottin Goguet F. How SLX4 cuts through the mystery of HIV-1 Vpr-mediated cell cycle arrest. Retrovirology. 2014;11:117 pubmed publisher
    ..We will also discuss how these findings open new questions towards the understanding of the biological function of Vpr regarding innate immune sensing. ..
  30. Fugger K, Chu W, Haahr P, Kousholt A, Beck H, Payne M, et al. FBH1 co-operates with MUS81 in inducing DNA double-strand breaks and cell death following replication stress. Nat Commun. 2013;4:1423 pubmed publisher
    ..Accordingly, MUS81 and EME1-depleted cells show increased resistance to the cytotoxic effects of replication stress...
  31. Tomoda Y, Katsura M, Okajima M, Hosoya N, Kohno N, Miyagawa K. Functional evidence for Eme1 as a marker of cisplatin resistance. Int J Cancer. 2009;124:2997-3001 pubmed publisher
    ..Here, we demonstrate that Eme1 levels can predict cisplatin sensitivity more accurately than ERCC1 or Rad51 levels in a variety of human cancer ..
  32. Chang J, Kim J, Choi J, Lee J, Cho Y. Crystal structure of the Mus81-Eme1 complex. Genes Dev. 2008;22:1093-106 pubmed publisher
    The Mus81-Eme1 complex is a structure-specific endonuclease that plays an important role in rescuing stalled replication forks and resolving the meiotic recombination intermediates in eukaryotes...
  33. Laguette N, Brégnard C, Hue P, Basbous J, Yatim A, Larroque M, et al. Premature activation of the SLX4 complex by Vpr promotes G2/M arrest and escape from innate immune sensing. Cell. 2014;156:134-45 pubmed publisher
    ..induced the recruitment of VPRBP and kinase-active PLK1, enhancing the cleavage of DNA by SLX4-associated MUS81-EME1 endonucleases...
  34. Matos J, Blanco M, Maslen S, Skehel J, West S. Regulatory control of the resolution of DNA recombination intermediates during meiosis and mitosis. Cell. 2011;147:158-72 pubmed publisher
    ..Mitotic regulation thereby facilitates chromosome segregation while limiting the potential for loss of heterozygosity and sister-chromatid exchanges. ..
  35. Ciccia A, Ling C, Coulthard R, Yan Z, Xue Y, Meetei A, et al. Identification of FAAP24, a Fanconi anemia core complex protein that interacts with FANCM. Mol Cell. 2007;25:331-43 pubmed
    ..Our data indicate that the FANCM/FAAP24 complex may play a key role in recruitment of the FA core complex to damaged DNA. ..
  36. Cohen E. From arrest to escape: HIV-1 Vpr cuts a deal. Cell Host Microbe. 2014;15:125-7 pubmed publisher
    ..In a recent issue of Cell, Laguette et al. (2014) demonstrate that untimely activation of the structure-specific endonuclease regulator SLX4 complex by Vpr promotes G2/M arrest and escape from innate immune sensing. ..
  37. Gwon G, Kim Y, Liu Y, Watson A, Jo A, Etheridge T, et al. Crystal structure of a Fanconi anemia-associated nuclease homolog bound to 5' flap DNA: basis of interstrand cross-link repair by FAN1. Genes Dev. 2014;28:2276-90 pubmed publisher
    ..The PaFAN1 structure provides insights into how archaeal Holliday junction resolvases evolved to incise 5' flap substrates and how FAN1 integrates with the FA complex to participate in ICL repair. ..
  38. Berger G, Lawrence M, Hué S, Neil S. G2/M cell cycle arrest correlates with primate lentiviral Vpr interaction with the SLX4 complex. J Virol. 2015;89:230-40 pubmed publisher
    ..immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) mediates this through activation of the SLX4/MUS81/EME1 exonuclease complex that forms part of the Fanconi anemia DNA repair pathway...
  39. Forment J, Blasius M, Guerini I, Jackson S. Structure-specific DNA endonuclease Mus81/Eme1 generates DNA damage caused by Chk1 inactivation. PLoS ONE. 2011;6:e23517 pubmed publisher
    ..breaks at replication forks when Chk1 activity is compromised relies on the DNA endonuclease complex Mus81/Eme1. Importantly, we show that Mus81/Eme1-dependent DNA damage--rather than a global increase in replication-fork ..
  40. Nair N, Castor D, MacArtney T, Rouse J. Identification and characterization of MUS81 point mutations that abolish interaction with the SLX4 scaffold protein. DNA Repair (Amst). 2014;24:131-137 pubmed publisher
    MUS81-EME1 is a conserved structure-selective endonuclease with a preference for branched DNA substrates in vitro that correspond to intermediates of DNA repair...
  41. Brégnard C, Benkirane M, Laguette N. DNA damage repair machinery and HIV escape from innate immune sensing. Front Microbiol. 2014;5:176 pubmed publisher
    ..Within this review we discuss the impact of this finding on our understanding of the interplay between HIV replication and nucleic acid metabolism and its implications for cancer-related chronic inflammation. ..
  42. Guenzel C, Hérate C, Benichou S. HIV-1 Vpr-a still "enigmatic multitasker". Front Microbiol. 2014;5:127 pubmed publisher
    ..In this review, we will summarize the main reported functions of HIV-1 Vpr and their significance in the context of the viral life cycle. ..
  43. Gwon G, Jo A, Baek K, Jin K, Fu Y, Lee J, et al. Crystal structures of the structure-selective nuclease Mus81-Eme1 bound to flap DNA substrates. EMBO J. 2014;33:1061-72 pubmed publisher
    The Mus81-Eme1 complex is a structure-selective endonuclease with a critical role in the resolution of recombination intermediates during DNA repair after interstrand cross-links, replication fork collapse, or double-strand breaks...
  44. Zhou X, Delucia M, Ahn J. SLX4-SLX1 Protein-independent Down-regulation of MUS81-EME1 Protein by HIV-1 Viral Protein R (Vpr). J Biol Chem. 2016;291:16936-16947 pubmed publisher
    Evolutionarily conserved structure-selective endonuclease MUS81 forms a complex with EME1 and further associates with another endonuclease SLX4-SLX1 to form a four-subunit complex of MUS81-EME1-SLX4-SLX1, coordinating distinctive ..
  45. Ouyang J, Garner E, Hallet A, Nguyen H, Rickman K, Gill G, et al. Noncovalent interactions with SUMO and ubiquitin orchestrate distinct functions of the SLX4 complex in genome maintenance. Mol Cell. 2015;57:108-22 pubmed publisher
    ..Thus, the interactions of SLX4 with SUMO and ubiquitin increase its affinity for factors recognizing different DNA lesions or telomeres, helping to direct the SLX4 complex in distinct functional contexts. ..
  46. Sánchez A, Gadaleta M, Limbo O, Russell P. Lingering single-strand breaks trigger Rad51-independent homology-directed repair of collapsed replication forks in the polynucleotide kinase/phosphatase mutant of fission yeast. PLoS Genet. 2017;13:e1007013 pubmed publisher
    ..Mre11 and Ctp1 (CtIP/Sae2) double-strand break (DSB) resection proteins, Rad52 DNA strand annealing protein, Mus81-Eme1 Holliday junction resolvase, and Rqh1 (BLM/WRN/Sgs1) DNA helicase...
  47. Zeng S, Xiang T, Pandita T, Gonzalez Suarez I, Gonzalo S, Harris C, et al. Telomere recombination requires the MUS81 endonuclease. Nat Cell Biol. 2009;11:616-23 pubmed publisher
    ..Thus, our results suggest that MUS81 is involved in the maintenance of ALT cell survival at least in part by homologous recombination of telomeres. ..
  48. Domínguez Kelly R, Martin Y, Koundrioukoff S, Tanenbaum M, Smits V, Medema R, et al. Wee1 controls genomic stability during replication by regulating the Mus81-Eme1 endonuclease. J Cell Biol. 2011;194:567-79 pubmed publisher
    ..Notably, the DDR induced by depletion of Wee1 critically depends on the Mus81-Eme1 endonuclease, and we found that codepletion of Mus81 and Wee1 abrogated the S phase delay...