Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol MUS81 contributors: mct/pgu - updated : 23-01-2019
HGNC name MUS81 endonuclease homolog (S. cerevisiae)
HGNC id 29814
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivesalivary gland   highly
Endocrineadrenal gland   highly
Hearing/Equilibriumear   highly
Lymphoid/Immunethymus   highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • helix-hairpin-helix DNA-binding domains in the N and C termini
  • a WH domain (its mutations greatly reduce binding of the isolated domain to DNA and impact on incision activity of MUS81-EME1/EME2 complexes)
  • C-terminal ERCC4 nuclease domain
    • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies homolog to yeast Mus81
    Homologene
    FAMILY
  • XPF family
    • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies,PML
    intracellular,nucleus,nucleolus
    text
  • localizes to nucleoli and to regions of DNA damage in human S-phase cells
  • localizes to ALT-associated promyelocytic leukaemia nuclear bodies and associates with telomeric DNA in ALT cells
    • basic FUNCTION
  • playing a role in resolving Holliday junctions that arise when DNA replication is blocked by damage or by nucleotide depletion
  • playing a role in the maintenance of genomic integrity and tumor suppression
  • playing a role in the processing of stalled replication fork intermediates
  • catalyzes with EME1 coordinate bilateral cleavage of model Holliday-junction structures
  • involved in the maintenance of alternative lengthening of telomeres cell survival at least in part by homologous recombination of telomeres
  • differential functions of MUS81 and the FA pathway in repair of DNA damage during replication in human cells
  • required for the restart of stalled replication forks and for genomic integrity
  • cleaves potentially stalled replication forks, which allows dissipation of the excessive supercoiling resulting from TOP1 inhibition, and replication fork progression
  • conserved heterodimeric endonuclease MUS81-EME1 plays an important role in the maintenance of genomic integrity in eukaryotic cells
  • controlled MUS81-EME1 activity provides a safeguard mechanism to resolve DNA intermediates that may remain after replication and require processing before mitosis
  • MUS81-EME2 catalyzed cleavage of nicked and gapped duplex deoxyribonucleic acids (DNAs), generating double-strand breaks
  • the G2/M functions of MUS81, such as the cleavage of recombination intermediates and fragile site expression, are promoted by MUS81-EME1
  • MUS81 endonuclease resolves recombination intermediates and mediates cellular responses to exogenous replicative stress
  • also regulates the rate of DNA replication during normal growth by promoting replication fork progression while reducing the frequency of replication initiation events
  • MUS81 plays a key role in determining the rate of DNA replication without activating a novel group of replication origins
  • mitotic DNA synthesis, termed MiDAS, requires the MUS81-EME1 endonuclease and a non-catalytic subunit of the Pol-delta complex, POLD3
  • MUS81-SLX4 activation during mitosis promotes targeted resolution of persistent replication intermediates, which safeguards chromosome segregation
  • MUS81 sumoylation is important for normal mitotic chromosome congression
  • MUS81 complex is crucial for preserving genome stability through the resolution of branched DNA intermediates in mitosis
  • genome stability depends mainly on the ability of cells to counteract targeting of branched intermediates by the MUS81/EME1 complex in S-phase, rather than on a correct MUS81 function in mitosis
  • is known to limit the occurrence of chromosomal instability by processing these unresolved loci during mitosis
  • MUS81 and ERCC4 are a subset of Structure-specific endonucleases (SSEs) that resolve aberrant replication structures
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • complexing with EME1 in a structure-specific nuclease that is capable of resolving fork structures
  • MUS81-EME1 heterodimer acting as an endonuclease that exhibits a high specificity for synthetic replication fork structures, and is critical for genomic stability and the response to DNA crosslink damage and replication blockade
  • binding BTBD12
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with EME1
  • MUS81–EME1 is recruited to replication centers following DNA damage, through interaction with UHRF1
  • may cooperate with ATRX in processing of Holliday junctions intermediates that are formed during the repair of double-stranded breaks or stalled replication forks
  • interacting with FANCB (MUS81 plays an important role in cell proliferation to suppress cell death when FANCB is missing, indicating a functional linkage between MUS81 and the FA pathway)
  • interacting with CHEK1 (CHEK1-mediated protection of replication forks from MUS81/EME1 even under otherwise unchallenged conditions is therefore vital to prevent uncontrolled fork collapse and ensure proper S-phase progression in human cells)
  • WEE1 interacting with MUS81 (novel role of WEE1 in controlling MUS81 and DNA replication in human cells)
  • double-strand breaks, observed upon oncogene over-expression, depend on the MUS81 endonuclease, which represents a parallel pathway collaborating with WRN to prevent cell death
  • both MUS81-EME1 and MUS81-EME2 increased the activity of FEN1, but FEN1 did not stimulate the activity of MUS81-EME1/EME2
  • FBXO18 helicase activity is required to eliminate cells with excessive replication stress through the generation of MUS81-induced DNA double-strand breaks
  • SLX1A, like MUS81-EME1, is required for repair of DNA interstrand crosslinks, but this role appears to be independent of Holliday junctions (HJs) cleavage
  • coordinated actions of SLX1A-BTBD12 and MUS81-EME1 for Holliday junction resolution
  • GEN1 and the BTBD12-associated nucleases MUS81 and SLX1A are essential for the resolution of replication-induced Holliday junctions
  • RAD52/MUS81-dependent mechanism promoting cell viability and genome integrity in checkpoint-deficient cells, and disclose the involvement of MUS81 to multiple processes after replication stress
  • MUS81-EME2 protein, whose actions are restricted to S phase, is also responsible for telomere maintenance in telomerase-negative ALT (Alternative Lengthening of Telomeres) cells
  • MUS81 function in DNA interstrand crosslinks (ICL) repair requires interaction with SLX4
  • ATRX and MUS81 mammalian proteins physically interact and are important for the homologous recombination DNA repair pathway
  • MUS81 nuclease is constitutively active throughout the cell cycle but requires association with SLX4 for efficient substrate targeting
  • RECQL5 removes RAD51 filaments stabilizing stalled replication forks at common fragile sites (CFSs) and hence facilitates CFS cleavage by MUS81-EME1
  • replication fork progression in BRCA2-deficient cells requires MUS81
  • MUS81 provides likely a mechanism of replication stress tolerance, which sustains survival of BRCA2-deficient cells
  • EZH2 localizes at stalled forks where it methylates Lys27 on histone 3 (H3K27me3), mediating recruitment of the MUS81 nuclease
  • phosphorylated MUS81 interacts with SLX4, and this association promotes the function of the MUS81 complex
    • cell & other
    REGULATION
    Phosphorylated by CK2 kinase that phosphorylates MUS81 at Serine 87 in late-G2/mitosis, and upon mild replication stress
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in gastric cancer tissues
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • might be a potential marker for the malignancy of gastric cancer
    • Therapy target
    SystemTypeDisorderPubmed
    cancer  
    dual inactivation of CHEK2 and MUS81 remarkably inhibits cancer
    ANIMAL & CELL MODELS