Affinage

MUS81

Structure-specific endonuclease subunit MUS81 · UniProt Q96NY9

Length
551 aa
Mass
61.2 kDa
Annotated
2026-06-10
100 papers in source corpus 52 papers cited in narrative 52 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MUS81 is the catalytic subunit of structure-selective endonuclease heterodimers that cleave branched DNA intermediates arising during recombination and DNA replication, thereby safeguarding genome duplication and chromosome segregation (PMID:11741546, PMID:12721304). It is enzymatically inert alone and requires dimerization with a non-catalytic partner—Eme1/Mms4 in yeast and EME1 or EME2 in humans—to form an active nuclease that preferentially cuts 3'-flaps, replication forks, and nicked Holliday junctions while cleaving intact four-stranded Holliday junctions only poorly, instead resolving HJs by a nick-and-counternick mechanism in which a nicked junction is the favored substrate (PMID:11641278, PMID:12721304, PMID:12686547, PMID:14527419). Crystal structures of the XPF-family Mus81-Eme1 complex define a nuclease domain plus HhH motifs and a 5'-end binding pocket that bends 3'-flap substrates to position the scissile strand at the active site, providing the structural basis for its cleavage specificity (PMID:18413719, PMID:24733841). The two human isoforms divide labor across the cell cycle: MUS81-EME2 is the more active, broader-specificity enzyme that cleaves and restarts replication forks during S phase, whereas MUS81-EME1 operates at the G2/M transition to resolve recombination intermediates and to express common fragile sites for faithful sister-chromatid disjunction (PMID:24371268, PMID:24813886, PMID:23811685). MUS81 nuclease activity is tightly gated by cell-cycle and checkpoint signaling: CDK1- and polo-like kinase (Cdc5)-dependent phosphorylation of the non-catalytic subunit, reinforced by DDK (Cdc7-Dbf4) and the Rtt107 scaffold, activates the enzyme in a restricted mitotic window, and at G2/M MUS81-EME1 assembles with SLX1-SLX4 into the SLX-MUS Holliday junction resolvase (PMID:22730299, PMID:28096179, PMID:24076221). Recruitment and activity are further controlled by checkpoint kinases (Cds1/Chk1/Wee1), by EZH2-deposited H3K27me3 at stalled forks, and by helicase partners including BLM and RECQ5, the latter clearing RAD51 filaments to license fragile-site cleavage (PMID:15805465, PMID:21859861, PMID:29035360, PMID:28575661). Through these activities MUS81 supports interstrand crosslink repair, replication fork restart in BRCA2-deficient cells, telomere maintenance in ALT cells, and meiotic crossover formation, and its DNA cleavage can generate cytosolic dsDNA that activates STING-dependent type I interferon signaling (PMID:17036055, PMID:29038425, PMID:19363487, PMID:14704204, PMID:27178469).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2001 High

    Establishing what MUS81 does at the molecular level required showing that it forms a heterodimeric endonuclease, which it does with Eme1/Mms4 to cleave branched DNA structures.

    Evidence In vitro HJ cleavage with purified fission and budding yeast complexes, plus human Mus81 endonuclease assays and genetic rescue by bacterial resolvase RusA

    PMID:11641278 PMID:11719193 PMID:11741546

    Open questions at the time
    • Initial assays emphasized HJ cleavage before the strong preference for forks/flaps was quantified
    • In vivo substrate identity not yet defined
  2. 2002 High

    The question of MUS81's true physiological substrate was addressed by showing it cleaves stalled/branched replication forks far more efficiently than intact Holliday junctions, redefining it as a fork-processing nuclease.

    Evidence In vitro cleavage of defined fork substrates with cleavage-site mapping plus genetic suppression of replication-stress sensitivity by RusA in fission yeast

    PMID:12084712 PMID:12473680

    Open questions at the time
    • Did not establish how the enzyme is recruited to forks in cells
    • Relative contribution of fork vs HJ cleavage in vivo unresolved
  3. 2003 High

    Quantitative substrate-preference and cleavage-site studies established MUS81-Eme1/Mms4 as a 3'-flap/nicked-HJ-selective nuclease using a nick-and-counternick mechanism, and genetic work defined a dedicated subset of meiotic crossovers requiring it.

    Evidence Substrate-preference and cleavage-site mapping with purified human and yeast complexes, kinetic nick-and-counternick analysis, and meiotic crossover-class genetics in yeast

    PMID:12686547 PMID:12721304 PMID:12724407 PMID:12750322 PMID:14527419 PMID:14527420 PMID:14704204

    Open questions at the time
    • Whether intact dHJs are physiological substrates remained contested
    • Structural basis of nicked-HJ preference not yet visualized
  4. 2006 High

    Linking MUS81 to specific repair pathways in mammals, it was shown to generate ICL- and replication-stress-induced DSBs and to act with RAD54 in homologous recombination.

    Evidence Co-IP of Mus81-Rad54, DSB detection and fork-recovery assays in Mus81-knockout mouse ES cells with double-mutant epistasis

    PMID:17036055 PMID:17934473

    Open questions at the time
    • Direct in vivo substrate at stalled forks not visualized
    • Did not separate beneficial fork restart from deleterious fork breakage
  5. 2008 High

    Crystal structures and rigorous enzymology resolved how MUS81-Eme1 recognizes branched DNA and confirmed it as a catalytically defined structure-selective endonuclease, including coordinated bilateral HJ cleavage by the human enzyme.

    Evidence X-ray crystallography of fission yeast Mus81-Eme1 with structure-function mutagenesis, full kinetic characterization of budding yeast Mus81-Mms4, and cruciform-cleavage kinetics of human enzyme

    PMID:18281703 PMID:18310322 PMID:18413719

    Open questions at the time
    • Substrate-bound structure of the human enzyme not yet available
    • How phosphorylation activates the enzyme structurally unknown
  6. 2009 High

    A specialized genome-maintenance role emerged with the finding that MUS81 supports telomere recombination in ALT cancer cells through its endonuclease activity and TRF2 interaction.

    Evidence Colocalization with APBs, telomere ChIP, Co-IP of MUS81-TRF2, and siRNA depletion with proliferation/recombination readouts in ALT cells

    PMID:19363487

    Open questions at the time
    • Which EME partner mediates telomeric activity was not resolved here
    • Mechanism of TRF2 regulation of nuclease activity undefined
  7. 2011 High

    The checkpoint context of MUS81 fork cleavage was clarified by showing that Chk1/Wee1 restraint prevents MUS81-Eme1 from breaking forks, and that MUS81 cleaves CPT-stalled forks while also aiding fork progression.

    Evidence Co-IP of Wee1-Mus81, codepletion epistasis, gammaH2AX DSB assays, and DNA combing in human cells

    PMID:21858151 PMID:21859861 PMID:22123861

    Open questions at the time
    • Did not distinguish EME1 vs EME2 contributions to the checkpoint-restrained activity
    • Direct kinase target on MUS81 complex not mapped here
  8. 2012 High

    The regulatory logic of mitotic MUS81 activation was established: CDK- and Cdc5-dependent phosphorylation of the non-catalytic Mms4 subunit switches on nuclease activity within a defined cell-cycle window without inducing multimerization.

    Evidence Cell-cycle-staged phosphorylation analysis, in vitro nuclease assays of phospho-defective mutants, and solution biophysics of oligomeric state in budding yeast

    PMID:22645308 PMID:22730299

    Open questions at the time
    • Full kinase complement and human conservation not yet established
    • Structural mechanism of phospho-activation unknown
  9. 2013 High

    MUS81-EME1 was placed in the SLX-MUS holoenzyme and shown to express common fragile sites in mitosis, integrating it into the in vivo Holliday-junction resolution and chromosome-segregation machinery.

    Evidence In vitro reconstitution of SLX-MUS, HJ cleavage assays, human and mouse genetics with synthetic-lethality and chromosome-segregation readouts, CFS localization and anaphase-bridge scoring, plus damage-induced CDK1/ATR phosphorylation of Eme1

    PMID:23531881 PMID:23584455 PMID:23811685 PMID:23811686 PMID:24076219 PMID:24076221 PMID:24080495

    Open questions at the time
    • How SLX-MUS assembly is spatially restricted to anaphase substrates was not fully resolved
    • Balance between SLX-MUS and GEN1 pathways in vivo incompletely defined
  10. 2014 High

    The two human isoforms were shown to divide labor temporally and biochemically, with MUS81-EME2 driving S-phase fork cleavage/restart and MUS81-EME1 driving G2/M recombination-intermediate processing and fragile-site expression.

    Evidence Comparative in vitro cleavage of purified MUS81-EME1 vs MUS81-EME2, isoform-specific siRNA depletion with cell-cycle-staged fork-restart and ALT assays, and crystal structures of human Mus81-Eme1 bound to 3'-flap DNA

    PMID:24371268 PMID:24733841 PMID:24813886

    Open questions at the time
    • How EME2 is selectively recruited in S phase remains unclear
    • Structural basis of EME2's broader specificity not determined
  11. 2015 High

    MUS81 was shown to shape normal and broken-fork replication dynamics—limiting template switching and mutagenic synthesis while tuning fork speed and initiation frequency.

    Evidence Genetic analysis with repair-product sequencing for template switching plus DNA fiber/origin-mapping in Mus81-deficient cells

    PMID:25879486 PMID:26273056

    Open questions at the time
    • Substrate(s) at unperturbed forks not directly defined
    • How MUS81 distinguishes productive from harmful cleavage during normal growth unclear
  12. 2017 High

    Recruitment and activation mechanisms at stalled forks were elaborated, including EZH2/H3K27me3-mediated targeting, DDK/Rtt107 activation, RECQ5-assisted fragile-site cleavage, and a key role in BRCA2-deficient fork restart.

    Evidence ChIP and Co-IP linking EZH2/H3K27me3 to MUS81, in vitro kinase reconstitution with DDK/Cdc5 and Rtt107 scaffold mapping, RECQ5-MUS81 Co-IP with phospho-mapping and CFS assays, and nuclease-dead/fork-resection epistasis in BRCA2-deficient cells

    PMID:28096179 PMID:28575661 PMID:28714477 PMID:29035360 PMID:29038425

    Open questions at the time
    • Hierarchy among the multiple recruitment routes (histone mark, scaffold, helicase) not integrated
    • Therapeutic window for MUS81 inhibition in BRCA-deficient tumors undefined
  13. 2019 High

    A feedback regulatory circuit was uncovered in which MUS81 cleavage of reversed forks and R-loops triggers ATR activation, while ATR in turn restrains excessive MUS81 cleavage.

    Evidence siRNA depletion, ATR inhibition, R-loop modulation, and reversed-fork/checkpoint analysis in human cells

    PMID:31708417

    Open questions at the time
    • Molecular target of ATR-mediated MUS81 restraint not identified
    • Single-study circuit awaiting independent corroboration
  14. 2021 Low

    An enzymatic role for MUS81 in regulating WEE1 turnover via beta-TRCP and innate immune signaling was proposed in gastric cancer cells.

    Evidence Ubiquitination assays, beta-TRCP Co-IP, MUS81 knockdown/overexpression, and cGAS/STING activation assays (single lab)

    PMID:34625086

    Open questions at the time
    • Indirect mechanism linking endonuclease activity to WEE1 ubiquitination not resolved
    • Single lab, not independently confirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the cell selects between MUS81-EME1 and MUS81-EME2, integrates the multiple recruitment and activation inputs (CDK/PLK/DDK phosphorylation, SLX4 scaffold, H3K27me3, helicases, ATR feedback), and times cleavage to avoid catastrophic fork breakage remains incompletely defined.
  • No unified model integrating recruitment routes with isoform choice
  • Structural basis of phospho-activation and human EME2 specificity unresolved
  • In vivo substrate engagement at unperturbed forks not directly visualized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 7 GO:0016787 hydrolase activity 4 GO:0003677 DNA binding 3
Localization
GO:0005634 nucleus 4 GO:0000228 nuclear chromosome 2 GO:0005730 nucleolus 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
BLMEME1EME2RAD54RECQ5SLX1SLX4TRF2
Complex memberships
MUS81-EME1MUS81-EME2MUS81-MMS4 (yeast)SLX-MUS holoenzyme (SLX1-SLX4-MUS81-EME1)

Evidence

Reading pass · 52 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Fission yeast Mus81 and Eme1 form a heterodimeric endonuclease complex that resolves Holliday junctions into linear duplex products in vitro. Mus81 and Eme1 are required during meiosis at a late step of meiotic recombination, and the mus81 meiotic defect is rescued by expression of a bacterial Holliday junction resolvase. In vitro Holliday junction cleavage assay with purified complex, genetic rescue by bacterial resolvase RusA, genetic epistasis Cell High 11719193
2001 Human Mus81 has associated endonuclease activity against structure-specific oligonucleotide substrates including synthetic Holliday junctions, cleaving them into linear duplexes by cutting across the junction exclusively on strands of like polarity. Immunoaffinity purification of human Mus81, in vitro endonuclease assay on Holliday junction and replication fork substrates Molecular cell High 11741546
2000 Fission yeast Mus81 interacts with the FHA1 domain of checkpoint kinase Cds1 (Chk2 ortholog). Mus81 enables survival of deoxyribonucleotide triphosphate starvation, UV radiation, and DNA polymerase impairment. Mus81 is essential in the absence of the Rqh1 (BLM) helicase and is required for meiosis. Genetic epistasis places Mus81 in the recombination pathway. Two-hybrid interaction, genetic epistasis, deletion mutant phenotyping Molecular and cellular biology Medium 11073977
2000 Budding yeast MUS81 protein contains helix-hairpin-helix motifs and XPF endonuclease homology domain. Deletion of MUS81 causes sensitivity to MMS and UV but not gamma-radiation or HO-induced DSBs. Mus81p and Rad54p interact by co-immunoprecipitation, and double mutant analysis places them in the same pathway for UV damage repair. Yeast two-hybrid screen (Rad54 as bait identified Mus81), immunoprecipitation, deletion mutant sensitivity assays, genetic epistasis Molecular & general genetics Medium 10905349
2001 Budding yeast Mms4 and Mus81 form a heterodimeric structure-specific endonuclease. Both subunits are required for optimal expression, substrate binding, and nuclease activity. The complex is 25-fold more active on branched duplex DNA and replication fork substrates than simple Y-forms. Synthetic lethality of sgs1 or top3 mutations with mus81 or mms4 requires MMS4/MUS81 for viability. Biochemical purification of Mms4-Mus81 heterodimer, in vitro nuclease activity assay on branched substrates, genetic synthetic lethality analysis Genes & development High 11641278
2002 Purified fission yeast Mus81-Eme1 and budding yeast Mus81-Mms4 cleave replication fork structures poorly or not at all for normal forks, but efficiently cleave forks where leading and/or lagging strands are juxtaposed at the junction, or forks with single-stranded tails. Cleavage sites map 3–6 bp 5' of the junction, predominantly on the leading strand template. In vitro cleavage assay with purified recombinant Mus81-Eme1 and Mus81-Mms4 on defined fork substrates The Journal of biological chemistry High 12473680
2002 Fission yeast Mus81-Eme1 endonuclease processes stalled replication forks: hypersensitivity of mus81, eme1, and rqh1 mutants to replication-stalling agents is suppressed by RusA HJ resolvase, and synthetic lethality of mus81 rqh1 double mutants is also suppressed by RusA. Recombinant Mus81-Eme1 readily cleaves replication fork structures but cleaves synthetic Holliday junctions poorly. Genetic suppression by bacterial resolvase RusA, in vitro cleavage assays with purified recombinant Mus81-Eme1 The Journal of biological chemistry High 12084712
2003 Human Mus81-Eme1 is a heterodimeric endonuclease that exhibits high specificity for replication fork structures and 3'-flap DNA in vitro, cleaving Holliday junctions approximately 75-fold less efficiently than flap or fork structures. Cleavage of Holliday junctions can be increased 6-fold by homologous sequences permitting base pair breathing. Purification of human Mus81-Eme1 heterodimer, in vitro cleavage assays on synthetic replication fork, 3'-flap, and Holliday junction substrates The Journal of biological chemistry High 12721304
2003 Human MMS4 (hMMS4) is identified as the binding partner of human MUS81. hMUS81 or hMMS4 alone have no detectable nuclease activity, but the hMUS81-hMMS4 complex is a structure-specific nuclease capable of resolving fork structures. Immunoaffinity purification, in vitro nuclease assay comparing individual subunits vs. heterodimer The Journal of biological chemistry High 12686547
2003 Fission yeast Mus81-Eme1 preferentially cleaves junctions that mimic intermediates formed during the transition from double-strand break to double Holliday junction (nicked Holliday junctions and 3'-flap structures), cleaving them in precisely the right orientation to guarantee crossover formation. In vitro cleavage assay with purified Mus81-Eme1 on defined meiotic recombination intermediate substrates, genetic analysis of meiotic crossovers Molecular cell High 14527420
2003 Endogenous fission yeast Mus81-Eme1 resolves Holliday junctions by a nick-and-counternick mechanism: a nicked HJ is the preferred substrate, cleavage occurs on the strand opposing the nick, and resolving cuts on intact HJs are quasi-simultaneous with a large rate enhancement of the second cut due to the flexible nicked HJ intermediate. In vitro cleavage assays with endogenous and recombinant Mus81-Eme1 on nicked and intact HJ substrates, kinetic analysis Molecular cell High 14527419
2003 The Mus81-Mms4 cleavage site in S. cerevisiae is determined by the 5' end of the DNA strand at the flap junction (5 nt 5' of the flap), not by the branch point. Substrates lacking a 5' end within 4 nt of the flap are cleaved poorly by Mus81-Mms4. This distinguishes it from Rad1-Rad10, which uses branch-point-based cleavage. In vitro cleavage site mapping with defined substrates, kinetic analysis Molecular and cellular biology High 12724407
2003 Fission yeast mus81 mutants have normal or elevated frequencies of gene conversion but 20- to 100-fold reduced frequencies of crossing over, demonstrating that gene conversion and crossing over can be genetically separated and that Mus81 is specifically required for meiotic crossing over. Genetic analysis of meiotic recombination frequencies in mus81 deletion mutants Genetics High 14704204
2003 Budding yeast Mus81/Mms4 is required for only a distinct subset (Class II) of meiotic crossovers that exhibit no interference and are independent of MSH4/MSH5. Class I crossovers (dependent on MSH4/MSH5, interference-sensitive) are unaffected by MUS81/MMS4 deletion. Double Holliday junction intermediates are reduced (not accumulated) in mms4 mutants, arguing against Mus81/Mms4 being the major meiotic dHJ resolvase. Genetic analysis of crossover classes, interference analysis, dHJ intermediate analysis in mms4 mutants, RusA expression rescue experiments Genetics High 12750322
2005 Fission yeast Cds1 (checkpoint kinase) phosphorylates Mus81 in a manner dependent on the FHA-binding motif of Mus81. A mutation eliminating this Cds1-binding/phosphorylation site exacerbates deletion mutator phenotypes and causes hyper-recombination in HU-treated cells. In acute HU arrest, Mus81 undergoes extensive Cds1-dependent phosphorylation and dissociates from chromatin, preventing cleavage of stalled forks. In replication mutants at semipermissive conditions, Mus81 undergoes minor Cds1-dependent phosphorylation and remains chromatin-associated. Chromatin fractionation, phosphorylation assays, FHA-binding motif mutagenesis, genetic analysis of deletion mutator phenotype Genes & development High 15805465
2006 Mouse Mus81-Eme1 is involved in generating ICL-induced double-strand breaks in ES cells during S phase. Generation of DSBs from forks stalled by single-strand-affecting damage did not require Mus81. Mus81 physically interacts with the HR protein Rad54, and Mus81−/−Rad54−/− ES cells were as hypersensitive to ICL agents as Mus81−/− cells, placing them in the same pathway. Co-immunoprecipitation of Mus81-Rad54, DSB detection in Mus81−/− ES cells, double mutant sensitivity analysis The EMBO journal High 17036055
2007 Mammalian Mus81 is involved in the formation of double-strand DNA breaks in response to inhibition of replication. In the absence of Mus81-dependent chromosome processing, recovery of stalled DNA replication forks is attenuated and chromosomal aberrations arise. Mus81-knockout mouse cells, DSB detection, replication fork recovery assays, cytogenetic analysis Nature structural & molecular biology High 17934473
2008 Crystal structure of the fission yeast Mus81-Eme1 complex was determined. Both subunits have a central nuclease domain, two HhH motifs at the C-terminus, and a linker helix. A flexible intradomain linker (36 residues) in the Eme1 nuclease domain is essential for DNA recognition. Basic residues lining the active site cleft of Mus81 interact with the flexible arm of a nicked Holliday junction, providing the structural basis for the nick-and-counternick mechanism and preference for nicked HJ. X-ray crystallography of Mus81-Eme1 complex, structure-function mutagenesis Genes & development High 18413719
2008 Kinetic analysis (kcat, Km) of S. cerevisiae Mus81-Mms4 demonstrates it is a catalytically active structure-selective endonuclease with three substrate classes: Class I (low Km, high kcat) = nicked HJ, 3'-flap, and replication fork-like structures; Class II (low Km, low kcat) = D-loop and partial HJ; Class III (high Km, low kcat) = splayed Y junction. Intact Holliday junctions are negligibly cut. Mus81-Mms4 exists in defined phosphorylated forms but neither modification state supports HJ incision in isolation. Classical enzymological characterization with purified Mus81-Mms4, kinetic analysis Nucleic acids research High 18281703
2008 Human Mus81-Eme1 catalyzes coordinate bilateral cleavage of model Holliday junction structures in a sequential manner within the lifetime of the enzyme-substrate complex, resulting in symmetrical cleavage of cruciform structures. Kinetic and enzymatic analysis with purified recombinant enzyme, 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 (amino acids 125–244 of Mus81 interact with C-terminal region aa 1007–1417 of BLM) and stimulates Mus81-Eme1 endonuclease activity on nicked Holliday junctions and 3'-flap structures by enhancing Mus81 DNA binding. BLM colocalizes with Mus81 at stalled replication forks during S-phase arrest. BLM does not affect Mus81 helicase activity. Co-immunoprecipitation, domain mapping, in vitro nuclease stimulation assay, colocalization by fluorescence microscopy Cancer research Medium 15805243
2008 Human Rad54 stimulates Mus81-Eme1 endonuclease activity on various Holliday junction-like intermediates through specific protein-protein interactions. Stimulation depends on formation of specific Rad54-DNA complexes in the presence of ATP. Saccharomyces cerevisiae Rad54 does not stimulate human Mus81-Eme1, showing species specificity. In vitro nuclease stimulation assay with purified human Rad54 and Mus81-Eme1, species cross-reactivity testing Proceedings of the National Academy of Sciences of the United States of America Medium 19017809
2008 Human MUS81 localizes to nucleoli in S-phase cells and accumulates at sites of UV damage specifically in S-phase (not in cells blocked from replicating or that have completed replication), suggesting recruitment to sites where replication forks encounter damaged DNA. Immunofluorescence microscopy, colocalization with BLM and WRN, S-phase specific UV damage recruitment assay Molecular biology of the cell Medium 14638871
2009 MUS81 specifically localizes to ALT-associated PML nuclear bodies (APBs) and associates with telomeric DNA in ALT cells during G2 phase. Depletion of MUS81 reduces ALT-specific telomere recombination and causes proliferation arrest of ALT cells. The endonuclease activity of MUS81 is required for ALT cell survival. MUS81 interacts with TRF2, which regulates MUS81 endonuclease activity at telomeres. Fluorescence colocalization, ChIP for telomeric DNA, siRNA depletion, Co-IP of MUS81-TRF2, endonuclease activity assays Nature cell biology High 19363487
2011 Human Mus81-Eme1 is responsible for generating DSBs at replication forks stalled by topoisomerase I inhibition (camptothecin). Mus81 cleaves the stalled replication forks themselves rather than excising Top1 cleavage complexes. Mus81 also promotes efficient replication fork progression after CPT treatment (demonstrated by DNA combing). siRNA depletion of Mus81, DSB detection by γH2AX, DNA combing for fork progression analysis The Journal of cell biology High 22123861
2011 Human Mus81-Eme1 generates DNA damage upon Chk1 inhibition: the DDR induced by depletion of Wee1 critically depends on Mus81-Eme1 endonuclease, and codepletion of Mus81 and Wee1 abrogates the S-phase delay. Wee1 and Mus81 interact in vivo. Co-immunoprecipitation of Wee1-Mus81, codepletion experiments, H2AX phosphorylation assay, cell cycle analysis The Journal of cell biology Medium 21859861
2011 The structure-specific endonuclease Mus81/Eme1 is responsible for generating DNA double-strand breaks at replication forks when Chk1 activity is compromised. Mus81/Eme1-dependent DNA damage—rather than global replication fork stalling—is the cause of incomplete replication in Chk1-deficient cells. Mus81/Eme1 depletion alleviates S-phase progression defects associated with Chk1 deficiency. siRNA depletion of Mus81/Eme1 in Chk1-deficient cells, DSB assays, DNA replication assays PloS one High 21858151
2012 Budding yeast Mus81-Mms4 nuclease activity is strictly regulated by CDK (Cdc28)- and polo-like kinase (Cdc5)-dependent phosphorylation of the non-catalytic subunit Mms4. Phosphorylation occurs only after bulk DNA synthesis and before chromosome segregation and is absolutely required for Mus81-Mms4 function. A phosphorylation-defective mms4 mutant shows highly reduced nuclease activity. Cell-cycle-stage-specific phosphorylation analysis, in vitro nuclease assay with phosphorylation-defective mutants, genetic analysis Nucleic acids research High 22730299
2012 S. cerevisiae Mus81-Mms4 exists as a single heterodimer in solution and when bound to DNA substrates (not multimer). Cdc5 kinase activates Mus81-Mms4 nuclease activity on 3' flaps and Holliday junctions in vitro but does not induce multimerization. These data support a model in which Mus81-Mms4 cleaves nicked recombination intermediates (D-loops, nicked HJs, 3'-flaps) but not intact Holliday junctions with four uninterrupted strands. Solution biochemistry (analytical ultracentrifugation/SEC), in vitro nuclease assays with Cdc5, immunoprecipitation for multimerization Molecular and cellular biology High 22645308
2013 In response to CDK-mediated phosphorylation at the G2/M transition, SLX1-SLX4 and MUS81-EME1 associate to form a stable SLX-MUS holoenzyme. The reconstituted SLX-MUS complex is a Holliday junction resolvase that coordinates the active sites of two distinct endonucleases. SLX-MUS and GEN1 define two genetically distinct HJ resolution pathways in human cells. In vitro reconstitution of SLX-MUS holoenzyme, biochemical HJ cleavage assay, co-immunoprecipitation, cell depletion with chromosome segregation analysis Molecular cell High 24076221
2013 MUS81-EME1 localizes to common fragile site (CFS) loci in early mitotic cells and promotes cytological gaps/breaks at CFSs in metaphase chromosomes. MUS81-EME1-dependent CFS cleavage promotes faithful sister chromatid disjunction. Immunofluorescence colocalization with CFS markers, siRNA depletion, cytogenetic analysis of metaphase chromosome gaps Nature cell biology High 23811685
2013 ERCC1 and MUS81-EME1 colocalize with FANCD2 on mitotic chromosomes at CFS loci and process late replication intermediates/under-replicated DNA persisting at CFSs until mitosis. Depletion of either ERCC1 or MUS81-EME1 leads to increased chromosome bridges in anaphase, causing DNA damage in the subsequent G1 phase. Immunofluorescence colocalization on mitotic chromosomes, siRNA depletion, anaphase bridge scoring, γH2AX foci in G1 Nature cell biology High 23811686
2013 SLX1 and MUS81-EME1 act together to resolve HJs in human cells in a manner requiring tethering to the SLX4 scaffold. Both SLX1 and MUS81-EME1 are required for repair of DNA interstrand crosslinks, but the ICL repair role of SLX1 appears independent of HJ cleavage. Mouse genetics (Slx1/Slx4 knockout), structure-function analysis, HJ resolution assay in cells Molecular cell High 24076219
2013 SLX4-associated MUS81-EME1 and SLX1 are required for in vivo HJ resolution. GEN1 activity cannot substitute for SLX4-associated nucleases. Lack of BLM with SLX4 or GEN1 with SLX4 is synthetically lethal due to dysfunctional mitosis with unprocessed HJs. Human SLX4-null cell exploitation, synthetic lethality analysis, HJ resolution assay in vivo Cell reports High 24080495
2013 In budding yeast, premature activation of the Cdk1/Cdc5/Mus81-Mms4 pathway (via phosphomimetic Mms4 variants) induces crossover-associated chromosome translocations and precocious processing of damage-bypass sister chromatid junction intermediates. The Mus81-Mms4 pathway operates in a restricted G2/M temporal window, separate from Sgs1-Top3. Phosphomimetic Mms4 mutants, genetic analysis of crossover/translocation frequencies, epistasis The EMBO journal High 23531881
2013 Fission yeast Mus81-Eme1 HJ resolvase activity is activated by DNA damage through both Cdc2 (CDK1)- and Rad3 (ATR)-dependent phosphorylation of Eme1. This activation prevents gross chromosomal rearrangements in cells lacking Rqh1 helicase. Phosphorylation analysis of Eme1 in response to DNA damage, in vitro nuclease activity assay, genetic suppression of chromosomal rearrangements Nature structural & molecular biology High 23584455
2014 Human MUS81-EME2 is a more active endonuclease than MUS81-EME1 with broader substrate specificity. MUS81-EME2 cleaves 3'-flaps, replication forks, and nicked Holliday junctions like MUS81-EME1, but additionally cleaves D-loop recombination intermediates (disengaging the D-loop by cleaving the 3'-invading strand) and 5'-flap structures, activities not seen with MUS81-EME1. Purification of MUS81-EME2, comparative in vitro cleavage assays on defined substrates Nucleic acids research High 24371268
2014 Human MUS81-EME2 is responsible for fork cleavage and restart in S phase, while the G2/M functions of MUS81 (cleavage of recombination intermediates and fragile site expression) are promoted by MUS81-EME1. MUS81-EME2 is also responsible for telomere maintenance in ALT cells. siRNA depletion of EME1 vs. EME2, cell-cycle-staged replication fork restart assay, ALT telomere maintenance assay Cell reports High 24813886
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 bending of the 3'-flap substrate and placement of the incision strand at the active site, explaining the preference for 3'-flap DNA with 5' nicked ends. X-ray crystallography of human Mus81-Eme1 bound to multiple flap DNA substrates, biochemical and biophysical validation The EMBO journal High 24733841
2015 Mus81 endonuclease suppresses template switches between homologous sequences and diverged Alu repetitive elements during broken replication fork repair. Broken fork repair initially uses error-prone Pol32 (POLD3)-dependent synthesis, but mutagenic synthesis is limited to within a few kilobases from the break by Mus81 and a converging fork. Genetic analysis of Mus81 mutants, sequencing of repair products, measurement of template switch frequency Science High 26273056
2015 Mus81 regulates the rate of DNA replication during normal growth by promoting replication fork progression while reducing the frequency of replication initiation events. In the absence of Mus81 endonuclease activity, DNA synthesis is slowed and replication initiation events are more frequent, but without activation of novel replication origins. DNA fiber analysis, BrdU incorporation, replication origin mapping in Mus81-deficient cells Nature communications High 25879486
2016 MUS81 endonuclease cleaves genomic DNA leading to accumulation of cytosolic dsDNA in prostate cancer cells. This cytosolic DNA stimulates STING-dependent type I interferon expression and promotes phagocytic and T cell responses, resulting in immune rejection of tumor cells. Cytosolic DNA fractionation, MUS81 depletion/overexpression, STING signaling assays, immune cell recruitment assays Immunity High 27178469
2016 In Chk1-deficient cells, MUS81-EME2 (not MUS81-EME1) is responsible for generating nuclease-dependent DNA damage that triggers ATM pathway activation and modulates replication fork speed and origin usage. siRNA depletion of MUS81-EME2 vs. MUS81-EME1 in Chk1-deficient cells, DNA damage and replication dynamics assays Cell reports Medium 26804904
2017 EZH2 localizes to stalled replication forks and methylates Histone H3 Lys27 (H3K27me3), which mediates recruitment of MUS81 nuclease to stalled forks. Low EZH2 levels reduce H3K27 methylation, prevent MUS81 recruitment, and stabilize stalled forks, promoting PARP inhibitor resistance in BRCA2-deficient cells. ChIP for EZH2 and H3K27me3 at stalled forks, Co-IP of MUS81 with H3K27me3, siRNA depletion, fork stability assays Nature cell biology High 29035360
2017 In BRCA2-deficient cells, MRE11/CtIP-initiated and EXO1-extended resection of regressed fork arms creates ssDNA tails that serve as substrates for MUS81. MUS81 cleavage of these regressed forks promotes POLD3-dependent fork rescue, representing a replication fork restart mechanism. DNA fiber assay, siRNA depletion of MUS81/EXO1/MRE11, ssDNA substrate analysis Nature communications High 29038425
2017 DBF4-dependent kinase (DDK/Cdc7-Dbf4) phosphorylates Mus81-Mms4 in an interdependent manner with Cdc5. DDK-mediated phosphorylation of Mms4 is strictly required for Mus81 activation in mitosis. The scaffold protein Rtt107 binds the Mus81-Mms4 complex and interacts with Cdc7, targeting DDK and Cdc5 to enable full Mus81 activation. In vitro kinase assays, phosphorylation-defective mutant analysis, Co-IP, in vivo Mus81 nuclease activity assay The EMBO journal High 28096179
2017 RECQ5 helicase physically interacts with MUS81 and promotes MUS81-EME1-dependent cleavage of late replication intermediates at common fragile sites during early mitosis. This requires CDK1-dependent phosphorylation of RECQ5 at Ser727. RECQ5 removes inhibitory RAD51 filaments from stalled forks at CFSs, facilitating CFS cleavage by MUS81-EME1. Co-IP of RECQ5-MUS81, phosphorylation mapping, siRNA depletion, in vitro nuclease stimulation assay, CFS expression analysis Molecular cell High 28575661
2017 MUS81 nucleolytic activity is required to activate compensatory DNA synthesis during mitosis in BRCA2-deficient cells and to resolve mitotic interlinks, facilitating chromosome segregation. BRCA2-deficient cells rely on MUS81 for replication fork progression. Nuclease-dead MUS81 mutant expression, BrdU incorporation during mitosis, chromosome bridge scoring, fork progression analysis Nature communications High 28714477
2019 R loop-induced ATR activation requires MUS81 endonuclease (unlike ATR activation by replication inhibitors). ATR prevents excessive cleavage of reversed forks by MUS81, revealing a MUS81-triggered and ATR-mediated feedback loop regulating MUS81 activity at replication forks. siRNA depletion of MUS81, ATR inhibition, R-loop induction/suppression, reversed fork analysis, checkpoint activation assays Molecular cell High 31708417
2021 MUS81 regulates ubiquitination of WEE1 via the E3 ligase β-TRCP in an enzymatic (endonuclease activity-dependent) manner in gastric cancer cells. MUS81 inhibition elevates WEE1 expression and activates innate immune signaling via cGAS/STING pathway. Ubiquitination assay, β-TRCP co-immunoprecipitation, MUS81 knockdown/overexpression, cGAS/STING pathway activation assays Journal of experimental & clinical cancer research Low 34625086
2016 HIV-1 Vpr down-regulates both MUS81 and EME1 by hijacking the host CRL4-DCAF1 E3 ubiquitin ligase. This down-regulation is independent of SLX4-SLX1, and Vpr mutants lacking G2 arrest activity can still down-regulate MUS81-EME1, indicating these functions are separable. Co-immunoprecipitation, Vpr mutant analysis, proteasome inhibitor assays, SLX4-null cell analysis The Journal of biological chemistry Medium 27354282
2003 X-ray crystal structure of an archaeal XPF/Mus81 family nuclease (Hef) middle domain shows the nuclease domain architecture has remarkable similarity to restriction endonucleases, with GDX(n)ERKX(3)D motif corresponding to PDX(n)(E/D)XK in restriction enzymes. XPF/Rad1/Mus81/ERCC1 proteins form dimers through nuclease domain and HhH domain interfaces. X-ray crystallography, mutagenesis of dimerization interfaces, endonuclease activity assays Structure Medium 12679022

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Mus81-Eme1 are essential components of a Holliday junction resolvase. Cell 455 11719193
2017 MRE11 and EXO1 nucleases degrade reversed forks and elicit MUS81-dependent fork rescue in BRCA2-deficient cells. Nature communications 346 29038425
2007 The structure-specific endonuclease Mus81 contributes to replication restart by generating double-strand DNA breaks. Nature structural & molecular biology 327 17934473
2003 The Mus81/Mms4 endonuclease acts independently of double-Holliday junction resolution to promote a distinct subset of crossovers during meiosis in budding yeast. Genetics 312 12750322
2017 EZH2 promotes degradation of stalled replication forks by recruiting MUS81 through histone H3 trimethylation. Nature cell biology 284 29035360
2002 Alternate pathways involving Sgs1/Top3, Mus81/ Mms4, and Srs2 prevent formation of toxic recombination intermediates from single-stranded gaps created by DNA replication. Proceedings of the National Academy of Sciences of the United States of America 274 12475932
2001 Functional overlap between Sgs1-Top3 and the Mms4-Mus81 endonuclease. Genes & development 268 11641278
2013 Coordinated actions of SLX1-SLX4 and MUS81-EME1 for Holliday junction resolution in human cells. Molecular cell 261 24076221
2003 Generating crossovers by resolution of nicked Holliday junctions: a role for Mus81-Eme1 in meiosis. Molecular cell 259 14527420
2006 The structure-specific endonuclease Mus81-Eme1 promotes conversion of interstrand DNA crosslinks into double-strands breaks. The EMBO journal 245 17036055
2000 Damage tolerance protein Mus81 associates with the FHA1 domain of checkpoint kinase Cds1. Molecular and cellular biology 238 11073977
2013 ERCC1 and MUS81-EME1 promote sister chromatid separation by processing late replication intermediates at common fragile sites during mitosis. Nature cell biology 236 23811686
2008 Structural and functional relationships of the XPF/MUS81 family of proteins. Annual review of biochemistry 231 18518821
2013 MUS81 promotes common fragile site expression. Nature cell biology 230 23811685
2001 Human Mus81-associated endonuclease cleaves Holliday junctions in vitro. Molecular cell 229 11741546
2002 Mus81-Eme1 and Rqh1 involvement in processing stalled and collapsed replication forks. The Journal of biological chemistry 203 12084712
2000 MUS81 encodes a novel helix-hairpin-helix protein involved in the response to UV- and methylation-induced DNA damage in Saccharomyces cerevisiae. Molecular & general genetics : MGG 193 10905349
2016 The DNA Structure-Specific Endonuclease MUS81 Mediates DNA Sensor STING-Dependent Host Rejection of Prostate Cancer Cells. Immunity 184 27178469
2003 Identification and characterization of the human mus81-eme1 endonuclease. The Journal of biological chemistry 175 12721304
2015 DNA REPAIR. Mus81 and converging forks limit the mutagenicity of replication fork breakage. Science (New York, N.Y.) 167 26273056
2008 MUS81 generates a subset of MLH1-MLH3-independent crossovers in mammalian meiosis. PLoS genetics 164 18787696
2011 Wee1 controls genomic stability during replication by regulating the Mus81-Eme1 endonuclease. The Journal of cell biology 162 21859861
2004 Involvement of mammalian Mus81 in genome integrity and tumor suppression. Science (New York, N.Y.) 160 15205536
2003 The mechanism of Mus81-Mms4 cleavage site selection distinguishes it from the homologous endonuclease Rad1-Rad10. Molecular and cellular biology 159 12724407
2003 The endogenous Mus81-Eme1 complex resolves Holliday junctions by a nick and counternick mechanism. Molecular cell 149 14527419
2011 Mus81-mediated DNA cleavage resolves replication forks stalled by topoisomerase I-DNA complexes. The Journal of cell biology 143 22123861
2010 Mus81 and Yen1 promote reciprocal exchange during mitotic recombination to maintain genome integrity in budding yeast. Molecular cell 141 21172663
2008 RecQ helicase, Sgs1, and XPF family endonuclease, Mus81-Mms4, resolve aberrant joint molecules during meiotic recombination. Molecular cell 140 18691965
2013 Cooperative control of holliday junction resolution and DNA repair by the SLX1 and MUS81-EME1 nucleases. Molecular cell 127 24076219
2005 Disruption of murine Mus81 increases genomic instability and DNA damage sensitivity but does not promote tumorigenesis. Molecular and cellular biology 123 16107704
2013 Human GEN1 and the SLX4-associated nucleases MUS81 and SLX1 are essential for the resolution of replication-induced Holliday junctions. Cell reports 122 24080495
2019 ATR Protects the Genome against R Loops through a MUS81-Triggered Feedback Loop. Molecular cell 119 31708417
2008 Mus81/Mms4 endonuclease and Sgs1 helicase collaborate to ensure proper recombination intermediate metabolism during meiosis. Molecular cell 118 18691964
2014 Roles of SLX1-SLX4, MUS81-EME1, and GEN1 in avoiding genome instability and mitotic catastrophe. Genes & development 116 24831703
2013 Premature Cdk1/Cdc5/Mus81 pathway activation induces aberrant replication and deleterious crossover. The EMBO journal 115 23531881
2007 Exploring the roles of Mus81-Eme1/Mms4 at perturbed replication forks. DNA repair 114 17409028
2005 Replication checkpoint kinase Cds1 regulates Mus81 to preserve genome integrity during replication stress. Genes & development 109 15805465
2014 MUS81-EME2 promotes replication fork restart. Cell reports 107 24813886
2012 Cell cycle-dependent regulation of the nuclease activity of Mus81-Eme1/Mms4. Nucleic acids research 106 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
2008 Mus81 is essential for sister chromatid recombination at broken replication forks. The EMBO journal 95 18388861
2017 MUS81 nuclease activity is essential for replication stress tolerance and chromosome segregation in BRCA2-deficient cells. Nature communications 93 28714477
2008 Replication fork stalling in WRN-deficient cells is overcome by prompt activation of a MUS81-dependent pathway. The Journal of cell biology 93 18852298
2017 RECQ5 Helicase Cooperates with MUS81 Endonuclease in Processing Stalled Replication Forks at Common Fragile Sites during Mitosis. Molecular cell 91 28575661
2003 X-ray and biochemical anatomy of an archaeal XPF/Rad1/Mus81 family nuclease: similarity between its endonuclease domain and restriction enzymes. Structure (London, England : 1993) 90 12679022
2010 Functional overlap between the structure-specific nucleases Yen1 and Mus81-Mms4 for DNA-damage repair in S. cerevisiae. DNA repair 83 20106725
2009 Telomere recombination requires the MUS81 endonuclease. Nature cell biology 82 19363487
2013 Combinatorial regulation of meiotic holliday junction resolution in C. elegans by HIM-6 (BLM) helicase, SLX-4, and the SLX-1, MUS-81 and XPF-1 nucleases. PLoS genetics 81 23901331
2013 FBH1 co-operates with MUS81 in inducing DNA double-strand breaks and cell death following replication stress. Nature communications 80 23361013
2008 Saccharomyces cerevisiae Mus81-Mms4 is a catalytic, DNA structure-selective endonuclease. Nucleic acids research 80 18281703
2004 DNA repair by a Rad22-Mus81-dependent pathway that is independent of Rhp51. Nucleic acids research 78 15486206
2001 The fuss about Mus81. Cell 76 11733053
2005 Substrate specificity of the Saccharomyces cerevisiae Mus81-Mms4 endonuclease. DNA repair 75 15590332
2007 Cleavage of stalled forks by fission yeast Mus81/Eme1 in absence of DNA replication checkpoint. Molecular biology of the cell 68 18032583
2016 Signaling from Mus81-Eme2-Dependent DNA Damage Elicited by Chk1 Deficiency Modulates Replication Fork Speed and Origin Usage. Cell reports 65 26804904
2013 Survival of the replication checkpoint deficient cells requires MUS81-RAD52 function. PLoS genetics 65 24204313
2013 Joint molecule resolution requires the redundant activities of MUS-81 and XPF-1 during Caenorhabditis elegans meiosis. PLoS genetics 61 23874209
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
2007 Bloom's syndrome helicase and Mus81 are required to induce transient double-strand DNA breaks in response to DNA replication stress. Journal of molecular biology 59 18054789
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 59 16456034
2012 Distinct roles of Mus81, Yen1, Slx1-Slx4, and Rad1 nucleases in the repair of replication-born double-strand breaks by sister chromatid exchange. Molecular and cellular biology 58 22354996
2010 Overlapping roles for Yen1 and Mus81 in cellular Holliday junction processing. The Journal of biological chemistry 58 20178992
2015 The DNA repair endonuclease Mus81 facilitates fast DNA replication in the absence of exogenous damage. Nature communications 56 25879486
2012 Mus81-Mms4 functions as a single heterodimer to cleave nicked intermediates in recombinational DNA repair. Molecular and cellular biology 56 22645308
2008 Mus81-dependent double-strand DNA breaks at in vivo-generated cruciform structures in S. cerevisiae. Molecular cell 56 18922464
2009 Retracted: Cooperativity of Mus81.Mms4 with Rad54 in the resolution of recombination and replication intermediates. The Journal of biological chemistry 55 19129197
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
2003 Identification and characterization of human MUS81-MMS4 structure-specific endonuclease. The Journal of biological chemistry 54 12686547
2010 The archaeal Xpf/Mus81/FANCM homolog Hef and the Holliday junction resolvase Hjc define alternative pathways that are essential for cell viability in Haloferax volcanii. DNA repair 53 20667794
2017 Dbf4-dependent kinase and the Rtt107 scaffold promote Mus81-Mms4 resolvase activation during mitosis. The EMBO journal 52 28096179
2013 Substrate specificity of the MUS81-EME2 structure selective endonuclease. Nucleic acids research 49 24371268
2014 Controlling meiotic recombinational repair - specifying the roles of ZMMs, Sgs1 and Mus81/Mms4 in crossover formation. PLoS genetics 48 25329811
2009 The human Holliday junction resolvase GEN1 rescues the meiotic phenotype of a Schizosaccharomyces pombe mus81 mutant. Nucleic acids research 48 20040574
2005 Structural and functional analyses of an archaeal XPF/Rad1/Mus81 nuclease: asymmetric DNA binding and cleavage mechanisms. Structure (London, England : 1993) 47 16084390
2003 Mus81 endonuclease localizes to nucleoli and to regions of DNA damage in human S-phase cells. Molecular biology of the cell 46 14638871
2007 Synthetic lethality of Drosophila in the absence of the MUS81 endonuclease and the DmBlm helicase is associated with elevated apoptosis. Genetics 44 17603121
2005 BLM helicase facilitates Mus81 endonuclease activity in human cells. Cancer research 44 15805243
2012 The WRN and MUS81 proteins limit cell death and genome instability following oncogene activation. Oncogene 42 22410776
2003 RNA interference inhibition of Mus81 reduces mitotic recombination in human cells. Molecular biology of the cell 42 14617801
2014 Mus81-Mms4 and Yen1 resolve a novel anaphase bridge formed by noncanonical Holliday junctions. Nature communications 39 25466415
2004 An archaeal endonuclease displays key properties of both eukaryal XPF-ERCC1 and Mus81. The Journal of biological chemistry 36 15591065
2021 Targeting MUS81 promotes the anticancer effect of WEE1 inhibitor and immune checkpoint blocking combination therapy via activating cGAS/STING signaling in gastric cancer cells. Journal of experimental & clinical cancer research : CR 35 34625086
2016 STC2 as a novel mediator for Mus81-dependent proliferation and survival in hepatocellular carcinoma. Cancer letters 35 27939696
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
2008 Mus81, Rhp51(Rad51), and Rqh1 form an epistatic pathway required for the S-phase DNA damage checkpoint. Molecular biology of the cell 34 19037101
2005 Roles of SGS1, MUS81, and RAD51 in the repair of lagging-strand replication defects in Saccharomyces cerevisiae. Current genetics 34 16193328
2014 Crystal structures of the structure-selective nuclease Mus81-Eme1 bound to flap DNA substrates. The EMBO journal 33 24733841
2020 Homologous recombination and Mus81 promote replication completion in response to replication fork blockage. EMBO reports 32 32419301
2016 Disruption of SLX4-MUS81 Function Increases the Relative Biological Effectiveness of Proton Radiation. International journal of radiation oncology, biology, physics 32 27084631
2020 Mus81-Eme1-dependent aberrant processing of DNA replication intermediates in mitosis impairs genome integrity. Science advances 31 33298441
2013 Mus81 nuclease and Sgs1 helicase are essential for meiotic recombination in a protist lacking a synaptonemal complex. Nucleic acids research 31 23935123
2014 Human MUS81-EME2 can cleave a variety of DNA structures including intact Holliday junction and nicked duplex. Nucleic acids research 30 24692662
2015 Hold your horSSEs: controlling structure-selective endonucleases MUS81 and Yen1/GEN1. Frontiers in genetics 29 26284109
2013 Temporal regulation of the Mus81-Mms4 endonuclease ensures cell survival under conditions of DNA damage. Nucleic acids research 29 23901010
2017 Control of Mus81 nuclease during the cell cycle. FEBS letters 28 28640495
2007 Functional interplay of p53 and Mus81 in DNA damage responses and cancer. Cancer research 28 17875692

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