Affinage

EME1

Structure-specific endonuclease subunit EME1 · UniProt Q96AY2

Length
570 aa
Mass
63.3 kDa
Annotated
2026-04-28
48 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EME1 is the non-catalytic subunit of the MUS81-EME1 structure-selective endonuclease, a heterodimeric complex essential for processing branched DNA intermediates during replication stress, interstrand crosslink (ICL) repair, and meiotic recombination. MUS81-EME1 preferentially cleaves 3'-flap structures, replication fork intermediates, and nicked Holliday junctions via a nick-and-counternick mechanism, with substrate recognition driven by a flexible intradomain linker in EME1 and a hydrophobic wedge in MUS81 that bends DNA to position the scissile strand at the active site (PMID:12473680, PMID:14527419, PMID:24733841). The complex is cell-cycle regulated: CDK1-dependent phosphorylation of SLX4 drives assembly of an SLX-MUS holoenzyme at G2/M that resolves Holliday junctions and processes under-replicated DNA at common fragile sites, while direct phosphorylation of EME1 by CDK1 and ATR/Rad3 stimulates catalytic activity, and CK2-mediated phosphorylation of MUS81 promotes SLX4 interaction (PMID:24076221, PMID:23584455, PMID:29850896, PMID:36288699). Premature activation of MUS81-EME1 in S-phase—triggered by loss of Chk1 or Wee1—generates pathological double-strand breaks at replication forks, and EME1 functions redundantly with GEN1 for Holliday junction resolution in vivo, as combined loss causes embryonic lethality in mice (PMID:21858151, PMID:21859861, PMID:27383418).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2001 High

    Establishing that Mus81 and Eme1 form a heterodimeric endonuclease required for Holliday junction resolution and meiotic recombination answered the fundamental question of what nuclease resolves HJs in organisms lacking a canonical bacterial-type resolvase.

    Evidence Co-immunoprecipitation, in vitro HJ cleavage assay, genetic rescue with bacterial RusA resolvase in S. pombe

    PMID:11719193

    Open questions at the time
    • Substrate specificity beyond intact HJs was unknown
    • Whether a mammalian ortholog exists was unclear
    • Catalytic contribution of each subunit was undefined
  2. 2002 High

    Biochemical substrate profiling revealed that MUS81-EME1 preferentially cleaves replication fork structures and 3'-flaps rather than intact Holliday junctions, redefining it as a replication fork nuclease rather than a classical HJ resolvase, and genetic epistasis placed it parallel to the RecQ helicase Rqh1 in fork processing.

    Evidence In vitro endonuclease assays with purified recombinant enzyme on synthetic substrates; synthetic lethality and RusA suppression in S. pombe

    PMID:12084712 PMID:12473680

    Open questions at the time
    • How intact HJs are resolved in vivo remained unexplained
    • Mechanism of cleavage specificity was unknown at atomic level
  3. 2003 High

    Identification and biochemical characterization of the human EME1 ortholog, definition of the nick-and-counternick cleavage mechanism, demonstration of crossover-specific resolution, and knockout phenotypes collectively established that MUS81-EME1 is a conserved replication/recombination nuclease whose preferred substrates are nicked HJ-like intermediates and 3'-flaps, with critical roles in ICL repair and meiotic crossover formation.

    Evidence Purification of human MUS81-EME1 with quantitative substrate comparison; kinetic analysis of nick-and-counternick on nicked HJ substrates in S. pombe; Eme1 knockout ES cells with ICL hypersensitivity and spontaneous genomic instability; meiotic crossover analysis in mus81Δ

    PMID:12721304 PMID:14527419 PMID:14527420 PMID:14609959 PMID:14704204

    Open questions at the time
    • Structural basis for substrate recognition was unknown
    • Cell-cycle regulation of complex activity was not defined
    • Mammalian in vivo meiotic role of EME1 was untested
  4. 2006 High

    Placing MUS81-EME1 epistatically with Rad54 in the ICL repair pathway established that the endonuclease generates the double-strand breaks at stalled forks that initiate homologous recombination-mediated ICL bypass.

    Evidence Mus81−/− Rad54−/− double knockout mouse ES cells showing non-additive ICL sensitivity; DSB detection by pulsed-field gel electrophoresis

    PMID:17036055

    Open questions at the time
    • Direct stimulation of MUS81-EME1 by Rad54 had not been shown biochemically
    • Connection to Fanconi anemia pathway was unknown
  5. 2008 High

    Crystal structures of the MUS81-EME1 catalytic core, biochemical demonstration that Rad54 directly stimulates MUS81-EME1 HJ resolution activity, and evidence for bilateral cleavage within a single enzyme-substrate encounter provided the atomic and kinetic framework for understanding how the heterodimer recognizes and resolves branched DNA.

    Evidence X-ray crystallography with mutagenesis validation; in vitro reconstitution of Rad54-mediated stimulation with purified human proteins; kinetic analysis of coordinate bilateral cleavage

    PMID:18310322 PMID:18413719 PMID:19017809

    Open questions at the time
    • Structures of enzyme bound to DNA substrates were lacking
    • Cell-cycle regulatory phosphorylation had not been defined
  6. 2011 High

    Demonstrating that Chk1 and Wee1 each restrain MUS81-EME1 from cleaving replication forks in S-phase revealed that checkpoint kinases protect genomic integrity by preventing untimely MUS81-EME1 activation, not just by arresting the cell cycle.

    Evidence siRNA co-depletion epistasis with γH2AX quantification; Wee1-Mus81 co-immunoprecipitation; replication fork speed measurements

    PMID:21858151 PMID:21859861

    Open questions at the time
    • Whether restraint is via direct phosphorylation of MUS81 or EME1 was unclear
    • Connection to the SLX4 scaffold was not yet known
  7. 2012 High

    Showing that CDK and Polo-like kinase phosphorylate the non-catalytic subunit (Mms4/Eme1-equivalent) to activate nuclease activity at G2/M provided the first molecular explanation for cell-cycle-restricted resolution of recombination intermediates.

    Evidence Phosphorylation site mutagenesis of Mms4 in S. cerevisiae, in vitro nuclease assays of phospho-deficient mutants, cell-cycle timing analysis

    PMID:22730299

    Open questions at the time
    • Whether human EME1 is similarly phosphorylated was unknown
    • Higher-order complex assembly driven by phosphorylation was not yet defined
  8. 2013 High

    Discovery of the CDK-dependent SLX-MUS holoenzyme, direct phosphorylation of EME1 by CDK1 and ATR/Rad3, FANCA-mediated recruitment and stimulation for ICL incision, and MUS81-EME1 co-localization with FANCD2 at common fragile sites collectively established that MUS81-EME1 activity is orchestrated through multi-subunit assembly and multi-kinase phosphorylation to serve distinct genome maintenance functions at G2/M.

    Evidence In vitro reconstitution of SLX-MUS holoenzyme; Eme1 phospho-site mutagenesis with Cdc2/Rad3 kinase assays in S. pombe; purified FANCA stimulation of MUS81-EME1 on ICL substrates; immunofluorescence co-localization on mitotic chromosomes with siRNA depletion phenotypes

    PMID:23584455 PMID:23811686 PMID:24076219 PMID:24076221 PMID:24170812

    Open questions at the time
    • Structural basis of SLX4-MUS81 interaction was unknown
    • Relative contributions of SLX1 versus MUS81 active sites within the holoenzyme were debated
    • SUMO-dependent regulation was not yet characterized
  9. 2014 High

    Crystal structures of human MUS81-EME1 bound to 3'-flap DNA substrates revealed how a hydrophobic wedge and 5'-end binding pocket impose substrate specificity through DNA bending, answering the long-standing question of why the enzyme strongly prefers nicked and flapped over intact four-way junctions.

    Evidence X-ray crystallography of enzyme-DNA co-crystals with biochemical validation

    PMID:24733841

    Open questions at the time
    • Full-length complex with HJ substrate structure was lacking
    • How SLX4 binding alters substrate specificity was unknown
  10. 2016 High

    Genetic demonstration of redundancy between GEN1 and EME1 for in vivo HJ resolution (synthetic embryonic lethality in mice) and identification of HIV-1 Vpr-mediated CRL4-DCAF1-dependent degradation of MUS81-EME1 expanded the physiological and pathological contexts of EME1 function.

    Evidence Gen1/Eme1 double knockout mice with embryonic lethality; Vpr point mutant and DCAF1 depletion analysis

    PMID:27354282 PMID:27383418

    Open questions at the time
    • Whether Vpr-mediated degradation contributes to HIV pathogenesis in vivo was unknown
    • Tissue-specific requirements for EME1 versus GEN1 were unexplored
  11. 2018 High

    Identification of CK2 as the kinase phosphorylating MUS81 at Ser87 to promote SLX4 interaction at G2/M added a third kinase input to the cell-cycle timing mechanism and showed that premature phosphomimetic activation causes S-phase DSBs, unifying the theme that MUS81-EME1 must be temporally restrained.

    Evidence In vitro CK2 kinase assay, phospho-specific antibody, phosphomimetic/dead mutant expression with γH2AX detection and SLX4 co-IP

    PMID:29850896

    Open questions at the time
    • How CK2, CDK1, and ATR phosphorylation events are coordinated temporally was unclear
    • Whether CK2 phosphorylation of MUS81 affects catalytic rate or only scaffolding was not resolved
  12. 2020 High

    Showing that MUS81-EME1 aberrantly cleaves under-replicated DNA engaged in mitotic DNA synthesis upon Chk1 loss, and that nucleoside supplementation rescues this, clarified that MUS81-EME1-dependent chromosome instability arises from premature cleavage of incompletely replicated loci rather than from canonical recombination intermediates.

    Evidence siRNA depletion, mitotic DNA synthesis assay, chromosome segregation analysis, nucleoside rescue

    PMID:33298441

    Open questions at the time
    • Whether specific genomic loci are preferentially targeted was unknown
    • How Chk1 physically restrains MUS81-EME1 access to under-replicated DNA was not determined
  13. 2022 High

    NMR structure of phosphorylated SLX4MBR and identification of ATR-direct and Chk1-dependent phosphorylation plus SUMO-interaction motifs on EME1 completed the molecular picture of how cell-cycle kinases build the activation switch: CDK1-cyclin B phosphorylates SLX4 to fold an SAP domain that binds MUS81 and relaxes substrate specificity, while ATR/Chk1 phosphorylation of EME1 and SIMs in its N-terminus together stimulate catalytic activity.

    Evidence NMR structure of phospho-SLX4MBR, in vitro CDK1-cyclin B kinase assay with mutagenesis; Eme1 phospho-site and SIM mutagenesis with nuclease assays in S. pombe

    PMID:35452455 PMID:36288699

    Open questions at the time
    • Full reconstitution of the complete SLX-MUS holoenzyme with all phosphorylation marks has not been achieved
    • How SUMO-modified partners recruit EME1 via SIMs to specific genomic loci is undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: how the relative catalytic contributions of SLX1 and MUS81 active sites within the holoenzyme are coordinated on physiological substrates; what determines locus-specific targeting (e.g., fragile sites versus recombination intermediates); and how EME1 SUMO-interaction motifs integrate with the phosphorylation cascade to control spatiotemporal activation.
  • No full reconstitution of holoenzyme with all post-translational modifications on physiological chromatin substrates
  • Structural basis of SLX4-mediated coordination of two active sites unresolved
  • In vivo locus-specific targeting mechanism unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 7 GO:0016787 hydrolase activity 5 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 2 GO:0005694 chromosome 1
Pathway
R-HSA-1640170 Cell Cycle 5 R-HSA-69306 DNA Replication 4 R-HSA-73894 DNA Repair 4 R-HSA-1474165 Reproduction 3
Partners
FANCAMUS81RAD54BSLX1SLX4UHRF1WEE1
Complex memberships
MUS81-EME1 heterodimerSLX-MUS holoenzyme (SLX1-SLX4-MUS81-EME1)

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Mus81 and Eme1 form a heterodimeric endonuclease complex that resolves Holliday junctions into linear duplex products; both subunits are required for meiotic recombination at a late step, and the meiotic defect of mus81 is rescued by a bacterial HJ resolvase. Co-immunoprecipitation, in vitro endonuclease assay, genetic rescue with bacterial resolvase RusA Cell High 11719193
2002 Purified recombinant Mus81-Eme1 preferentially cleaves replication fork structures (particularly those with juxtaposed leading/lagging strands or single-stranded tails) but cleaves intact Holliday junctions poorly; cleavage occurs predominantly 3–6 bp 5' of the junction point on the leading strand template. In vitro endonuclease assay with purified recombinant protein on defined synthetic substrates, cleavage site mapping The Journal of biological chemistry High 12473680
2002 Mus81-Eme1 and the RecQ helicase Rqh1 act in parallel pathways to process stalled replication forks; mus81/eme1 and rqh1 double mutants are synthetically lethal, and this lethality is suppressed by RusA resolvase, placing both in HJ/fork-processing pathways. Genetic epistasis, synthetic lethality analysis, suppression by RusA resolvase The Journal of biological chemistry High 12084712
2003 Human EME1 was identified as the homolog of S. pombe Eme1; purified human Mus81-Eme1 heterodimer is an endonuclease with high specificity for synthetic replication fork structures and 3'-flaps in vitro, cleaving Holliday junctions ~75-fold less efficiently. Sequence homology cloning, purification of human Mus81-Eme1 heterodimer, in vitro endonuclease assays on multiple substrates The Journal of biological chemistry High 12721304
2003 Endogenous and recombinant fission yeast Mus81-Eme1 preferentially cleaves nicked Holliday junctions by a nick-and-counternick mechanism: cleavage occurs on the strand opposing the nick, and the second cut is greatly rate-enhanced by the flexibility of the nicked HJ intermediate. In vitro endonuclease assay with endogenous complex immunoprecipitated from yeast, cleavage site analysis, kinetic analysis Molecular cell High 14527419
2003 Purified fission yeast Mus81-Eme1 preferentially cleaves junctions mimicking the transition from DSB to double Holliday junction (nicked HJ-like structures) in an orientation that guarantees crossover formation, rather than intact dHJs. In vitro endonuclease assay with purified Mus81-Eme1, substrate mapping, meiotic genetic analysis Molecular cell High 14527420
2003 Mouse Eme1 forms a complex with Mus81 that preferentially cleaves 3'-flap structures and replication forks; Eme1−/− ES cells are hypersensitive to ICL agents (MMC, cisplatin) but show only mild sensitivity to IR, UV, and HU, and display spontaneous genomic instability. Gene targeting (Eme1 knockout), in vitro endonuclease assay with mouse Mus81-Eme1, sensitivity assays, SCE analysis The EMBO journal High 14609959
2003 Mus81 (and thus Mus81-Eme1) is required for meiotic crossing over but not gene conversion in fission yeast, genetically separating these two outcomes of homologous recombination. Genetic analysis of mus81 deletion mutants, measurement of crossover and gene conversion frequencies Genetics High 14704204
2006 Mus81 (Mus81-Eme1) generates ICL-induced DNA double-strand breaks in S phase in mouse ES cells; Mus81−/− Rad54−/− double-mutant cells show no additive ICL hypersensitivity, placing Mus81-Eme1 and Rad54-dependent HR in the same ICL repair pathway. Gene knockout, DSB detection assays (pulsed-field gel), epistasis analysis with Rad54 knockout, physical interaction (Co-IP of Mus81 and Rad54) The EMBO journal High 17036055
2008 Crystal structure of the Mus81-Eme1 complex reveals that both subunits contain a nuclease domain and two HhH motifs; a flexible 36-residue intradomain linker in the Eme1 nuclease domain is essential for DNA recognition; basic residues in the Mus81 active site cleft interact with the flexible arm of nicked HJ, providing structural basis for nick-and-counternick mechanism. X-ray crystallography, mutagenesis of active site and linker residues, biochemical endonuclease assays Genes & development High 18413719
2008 Human Mus81-Eme1 catalyzes coordinate bilateral (sequential) cleavage of Holliday junction structures within the lifetime of a single enzyme-substrate complex, with cooperative enzyme behavior enabling symmetric cleavage of cruciform substrates. Kinetic and enzymatic analysis of purified recombinant human Mus81-Eme1, self-limiting cruciform substrate assay Proceedings of the National Academy of Sciences of the United States of America High 18310322
2008 Human Rad54 physically interacts with Mus81 and stimulates Mus81-Eme1 endonuclease activity on Holliday junction-like intermediates; stimulation requires species-specific Rad54-Mus81 interaction and formation of specific Rad54-DNA complexes in the presence of ATP. Co-immunoprecipitation, in vitro endonuclease stimulation assay with purified proteins, cross-species comparison Proceedings of the National Academy of Sciences of the United States of America High 19017809
2008 STAT3 transcription factor binds the EME1 promoter in response to EGFR-src pathway activation by topoisomerase I inhibition, driving EME1 transcriptional upregulation and reduced DNA damage. Chromatin immunoprecipitation (ChIP) of STAT3 at EME1 promoter, reporter assays, EGFR/src pathway inhibition Cancer research Medium 18245483
2008 Mammalian Eme1 interacts with Np95 (an E3 ubiquitin ligase); co-localization on chromatin after camptothecin treatment is dependent on an intact RING finger of Np95, linking Mus81-Eme1 to replication-associated chromatin modification during the DNA damage response. Co-immunoprecipitation, co-localization by immunofluorescence, RING finger mutant analysis Biochemical and biophysical research communications Medium 18692478
2011 Wee1 kinase physically interacts with Mus81 in vivo; the DNA damage response (H2AX phosphorylation, replication fork slowing) induced by Wee1 depletion is dependent on Mus81-Eme1 endonuclease, and co-depletion of Mus81 and Wee1 abrogates the S-phase delay. Co-immunoprecipitation, siRNA co-depletion, H2AX phosphorylation assay, replication fork speed measurement The Journal of cell biology High 21859861
2011 Mus81/Eme1 endonuclease is responsible for generating DNA double-strand breaks at replication forks when Chk1 is inhibited; Mus81/Eme1 depletion alleviates S-phase progression defects caused by Chk1 deficiency, showing that Chk1 protects replication forks from Mus81/Eme1 cleavage. siRNA knockdown, γH2AX and DSB detection, S-phase progression assays, epistasis by co-depletion PloS one High 21858151
2012 Mus81-Mms4 (budding yeast ortholog with Eme1-equivalent Mms4) nuclease activity is regulated by CDK (Cdc28) and Polo-like kinase (Cdc5)-dependent phosphorylation of the Mms4 non-catalytic subunit specifically after bulk DNA synthesis and before chromosome segregation; phosphorylation-defective mms4 mutants show greatly reduced nuclease activity. Cell-cycle phosphorylation analysis, phosphorylation-defective mutant construction, in vitro nuclease assay, genetic sensitivity assays Nucleic acids research High 22730299
2013 In response to CDK-mediated phosphorylation at G2/M, SLX1-SLX4 and MUS81-EME1 associate to form a stable SLX-MUS holoenzyme that can be reconstituted in vitro; SLX-MUS acts as a HJ resolvase that coordinates the active sites of two distinct endonucleases, with more efficient and orchestrated HJ resolution than SLX1-SLX4 alone. Co-immunoprecipitation, in vitro reconstitution of SLX-MUS complex, HJ resolution biochemical assays, siRNA depletion with chromosome segregation phenotype Molecular cell High 24076221
2013 SLX1 and MUS81-EME1 act cooperatively in the same pathway (tethered by SLX4) to resolve Holliday junctions in mitotic cells; SLX4/SLX1 tethering is required for their cooperative HJ resolution function, and both are required for ICL repair. Mouse genetics (Slx1/Slx4 knockout), structure-function analysis, genetic epistasis, HJ resolution assays Molecular cell High 24076219
2013 DNA damage-induced activation of Mus81-Eme1 in fission yeast requires both Cdc2(CDK1)- and Rad3(ATR)-dependent phosphorylation of Eme1; this activation prevents gross chromosomal rearrangements in cells lacking Rqh1 helicase. Phosphorylation site mutagenesis of Eme1, kinase assays, chromosomal rearrangement assays, genetic epistasis with rqh1 deletion Nature structural & molecular biology High 23584455
2013 ERCC1 and MUS81-EME1 co-localize with FANCD2 on common fragile sites (CFSs) on mitotic chromosomes; depletion of either endonuclease impairs processing of under-replicated DNA at CFSs in mitosis, increasing chromosome bridges in anaphase and DNA damage in the following G1. Immunofluorescence co-localization on mitotic chromosomes, siRNA depletion, chromosome bridge quantification, γH2AX analysis Nature cell biology High 23811686
2013 FANCA interacts with MUS81 and recruits it to ICL lesions; purified FANCA greatly enhances MUS81-EME1-mediated ICL incision in vitro, with MUS81-EME1 incising at the 5' side of a psoralen ICL in fork structures. In vitro endonuclease assay with purified MUS81-EME1 and FANCA on ICL substrates, laser-induced ICL formation with Co-IP, truncation analysis of FANCA Nucleic acids research High 24170812
2014 Crystal structures of human Mus81-Eme1 bound to 3' flap DNA substrates reveal substrate-induced conformational changes: a hydrophobic wedge of Mus81 separates pre- and post-nick duplex DNA, and a '5' end binding pocket' hosts the 5' nicked end; these features drive sharp DNA bending and placement of the incision strand at the active site, explaining preference for 3' flap substrates with 5' nicked ends. X-ray crystallography of human Mus81-Eme1 bound to flap substrates, biochemical assays, biophysical analysis The EMBO journal High 24733841
2016 HIV-1 Vpr hijacks the host CRL4-DCAF1 E3 ubiquitin ligase to down-regulate both MUS81 and EME1; this down-regulation is independent of SLX4-SLX1 and independent of Vpr's G2 arrest activity. Co-immunoprecipitation, ubiquitin ligase pathway analysis, Vpr point mutants, siRNA depletion of DCAF1 The Journal of biological chemistry Medium 27354282
2016 Gen1 (GEN1) and Eme1 act redundantly for HJ resolution in vivo in mice; combined homozygous Gen1/Eme1 mutations cause synthetic lethality during early embryogenesis, and Gen1 loss makes Eme1 heterozygous MEFs more sensitive to DNA damage. Mouse genetics (double knockout), MEF sensitivity assays, meiotic recombination analysis DNA and cell biology High 27383418
2018 CK2 kinase phosphorylates MUS81 at Serine 87 in late-G2/mitosis and upon mild replication stress; phosphorylated MUS81 interacts with SLX4, and this promotes MUS81 complex function; expression of the phosphomimetic form causes DSB accumulation in S-phase due to unscheduled targeting of HJ-like intermediates. In vitro kinase assay, phospho-specific antibody, co-immunoprecipitation, phosphomimetic and phospho-dead mutant expression, γH2AX detection Nucleic acids research High 29850896
2020 Upon Chk1 depletion, Mus81-Eme1 aberrantly cleaves under-replicated DNA engaged in mitotic DNA synthesis, causing chromosome segregation defects and chromosomal instability; supplementing nucleosides to complete mitotic DNA synthesis restrains this Mus81-Eme1-dependent DNA damage. siRNA depletion, mitotic DNA synthesis assay, chromosome segregation analysis, nucleoside supplementation rescue Science advances High 33298441
2022 CDK1-cyclin B phosphorylates SLX4 at residues T1544, T1561, and T1571 in the MUS81-binding region (SLX4MBR); phosphorylated SLX4MBR drives folding of an SAP domain that mediates high-affinity interaction with MUS81, activates MUS81-EME1 by relaxing substrate specificity, and stimulates cleavage of replication and recombination structures. In vitro CDK1-cyclin B kinase assay, NMR structure of phosphorylated SLX4MBR, biochemical endonuclease activity assays, mutagenesis Cell reports High 36288699
2022 In fission yeast, direct phosphorylation of Eme1 by Rad3(ATR) kinase is essential for catalytic stimulation of Mus81-Eme1; Chk1-mediated phosphorylation of Eme1 also contributes to stimulation when combined with Rad3ATR phosphorylation; two SUMO-interacting motifs (SIMs) in the Eme1 N-terminal domain are also required for cell survival without Rqh1. Phosphorylation site mutagenesis of Eme1, in vitro kinase assays, SIM mutant analysis, nuclease activity assays, genetic viability assays PLoS genetics High 35452455

Source papers

Stage 0 corpus · 48 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Mus81-Eme1 are essential components of a Holliday junction resolvase. Cell 454 11719193
2003 Generating crossovers by resolution of nicked Holliday junctions: a role for Mus81-Eme1 in meiosis. Molecular cell 258 14527420
2013 Coordinated actions of SLX1-SLX4 and MUS81-EME1 for Holliday junction resolution in human cells. Molecular cell 255 24076221
2006 The structure-specific endonuclease Mus81-Eme1 promotes conversion of interstrand DNA crosslinks into double-strands breaks. The EMBO journal 243 17036055
2013 ERCC1 and MUS81-EME1 promote sister chromatid separation by processing late replication intermediates at common fragile sites during mitosis. Nature cell biology 235 23811686
2002 Mus81-Eme1 and Rqh1 involvement in processing stalled and collapsed replication forks. The Journal of biological chemistry 203 12084712
2003 Identification and characterization of the human mus81-eme1 endonuclease. The Journal of biological chemistry 175 12721304
2011 Wee1 controls genomic stability during replication by regulating the Mus81-Eme1 endonuclease. The Journal of cell biology 162 21859861
2003 The endogenous Mus81-Eme1 complex resolves Holliday junctions by a nick and counternick mechanism. Molecular cell 149 14527419
2013 Cooperative control of holliday junction resolution and DNA repair by the SLX1 and MUS81-EME1 nucleases. Molecular cell 122 24076219
2014 Roles of SLX1-SLX4, MUS81-EME1, and GEN1 in avoiding genome instability and mitotic catastrophe. Genes & development 114 24831703
2007 Exploring the roles of Mus81-Eme1/Mms4 at perturbed replication forks. DNA repair 114 17409028
2003 Eme1 is involved in DNA damage processing and maintenance of genomic stability in mammalian cells. The EMBO journal 114 14609959
2012 Cell cycle-dependent regulation of the nuclease activity of Mus81-Eme1/Mms4. Nucleic acids research 105 22730299
2002 Cleavage of model replication forks by fission yeast Mus81-Eme1 and budding yeast Mus81-Mms4. The Journal of biological chemistry 102 12473680
2003 Fission yeast Mus81.Eme1 Holliday junction resolvase is required for meiotic crossing over but not for gene conversion. Genetics 100 14704204
2011 Structure-specific DNA endonuclease Mus81/Eme1 generates DNA damage caused by Chk1 inactivation. PloS one 96 21858151
2007 Cleavage of stalled forks by fission yeast Mus81/Eme1 in absence of DNA replication checkpoint. Molecular biology of the cell 68 18032583
2008 Cleavage mechanism of human Mus81-Eme1 acting on Holliday-junction structures. Proceedings of the National Academy of Sciences of the United States of America 60 18310322
2006 Haploinsufficiency of the Mus81-Eme1 endonuclease activates the intra-S-phase and G2/M checkpoints and promotes rereplication in human cells. Nucleic acids research 58 16456034
2013 Regulation of Mus81-Eme1 Holliday junction resolvase in response to DNA damage. Nature structural & molecular biology 54 23584455
2008 Crystal structure of the Mus81-Eme1 complex. Genes & development 54 18413719
2008 The EGFR-STAT3 oncogenic pathway up-regulates the Eme1 endonuclease to reduce DNA damage after topoisomerase I inhibition. Cancer research 52 18245483
2009 Two distinct MUS81-EME1 complexes from Arabidopsis process Holliday junctions. Plant physiology 38 19339504
2016 SLX4-SLX1 Protein-independent Down-regulation of MUS81-EME1 Protein by HIV-1 Viral Protein R (Vpr). The Journal of biological chemistry 34 27354282
2008 Human Rad54 protein stimulates human Mus81-Eme1 endonuclease. Proceedings of the National Academy of Sciences of the United States of America 34 19017809
2014 Crystal structures of the structure-selective nuclease Mus81-Eme1 bound to flap DNA substrates. The EMBO journal 33 24733841
2020 Mus81-Eme1-dependent aberrant processing of DNA replication intermediates in mitosis impairs genome integrity. Science advances 31 33298441
2018 Phosphorylation by CK2 regulates MUS81/EME1 in mitosis and after replication stress. Nucleic acids research 23 29850896
2007 Mus81-Eme1-dependent and -independent crossovers form in mitotic cells during double-strand break repair in Schizosaccharomyces pombe. Molecular and cellular biology 23 17353272
2009 Functional evidence for Eme1 as a marker of cisplatin resistance. International journal of cancer 20 19267403
2011 Novel insights into maintaining genomic integrity: Wee1 regulating Mus81/Eme1. Cell division 19 22152133
2022 Phosphorylation of the DNA repair scaffold SLX4 drives folding of the SAP domain and activation of the MUS81-EME1 endonuclease. Cell reports 18 36288699
2008 Interplay between Np95 and Eme1 in the DNA damage response. Biochemical and biophysical research communications 16 18692478
2016 Gen1 and Eme1 Play Redundant Roles in DNA Repair and Meiotic Recombination in Mice. DNA and cell biology 12 27383418
2013 Damage-dependent regulation of MUS81-EME1 by Fanconi anemia complementation group A protein. Nucleic acids research 12 24170812
2021 Essential meiotic structure-specific endonuclease1 (EME1) promotes malignant features in gastric cancer cells via the Akt/GSK3B/CCND1 pathway. Bioengineered 10 34719326
2014 Cetuximab induces eme1-mediated DNA repair: a novel mechanism for cetuximab resistance. Neoplasia (New York, N.Y.) 10 24731284
2023 FIBP interacts with transcription factor STAT3 to induce EME1 expression and drive radioresistance in lung adenocarcinoma. International journal of biological sciences 9 37564211
2023 Identification of small-molecule inhibitors of human MUS81-EME1/2 by FRET-based high-throughput screening. Bioorganic & medicinal chemistry 7 37352577
2022 Regulation of Mus81-Eme1 structure-specific endonuclease by Eme1 SUMO-binding and Rad3ATR kinase is essential in the absence of Rqh1BLM helicase. PLoS genetics 4 35452455
2013 Effect of EME1 exon variant Ile350Thr on risk and early onset of breast cancer in southern Chinese women. Journal of biomedical research 4 23720674
2022 A protocol to determine the activities of human MUS81-EME1&2 endonucleases. STAR protocols 3 35819885
2025 SETD1A-dependent EME1 transcription drives PARPi sensitivity in HR deficient tumour cells. British journal of cancer 2 39994444
2025 Oncogenic EME1 promotes tumor progression and immune modulation in human cancers with therapeutic targeting potential. Discover oncology 1 41082058
2022 The Glu69Asp Polymorphism of EME1 Gene is Associated with an Increased Risk of Hepatocellular Carcinoma in Guangxi Population, China. International journal of general medicine 1 36281338
2026 Targeting EME1 Increases the Sensitivity of Camptothecin in Nasopharyngeal Carcinoma Cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 41532283
2025 LncRNA-EME1 enhances BRCA1 recruitment and alters repair of DNA damage in cervical cancer radioresistance. Non-coding RNA research 0 41113473