MUS81

Crossover junction endonuclease MUS81 is an enzyme that in humans is encoded by the MUS81 gene.^[5][6][7]

MUS81
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2MC3, 4P0P, 4P0Q, 4P0R, 4P0S
Identifiers
Aliases	MUS81, SLX3, MUS81 structure-specific endonuclease subunit
External IDs	OMIM: 606591; MGI: 1918961; HomoloGene: 5725; GeneCards: MUS81; OMA:MUS81 - orthologs
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q13.1 Start 65,857,126 bp[1] End 65,867,653 bp[1]
Gene location (Mouse) Chr. Chromosome 19 (mouse)[2] Band 19|19 A Start 5,532,373 bp[2] End 5,538,430 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in body of uterus left uterine tube muscle layer of sigmoid colon granulocyte mucosa of transverse colon right ovary canal of the cervix right coronary artery apex of heart left coronary artery Top expressed in muscle of thigh primary oocyte cerebellar cortex otic vesicle spermatocyte saccule granulocyte thymus superior frontal gyrus ventricular zone More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding nuclease activity endonuclease activity protein binding 3'-flap endonuclease activity metal ion binding hydrolase activity endodeoxyribonuclease activity crossover junction endodeoxyribonuclease activity Cellular component nucleoplasm nucleus nucleolus Holliday junction resolvase complex Biological process DNA recombination interstrand cross-link repair DNA catabolic process, endonucleolytic cellular response to DNA damage stimulus response to intra-S DNA damage checkpoint signaling DNA repair resolution of meiotic recombination intermediates double-strand break repair via break-induced replication mitotic G2 DNA damage checkpoint signaling replication fork processing mitotic intra-S DNA damage checkpoint signaling DNA metabolic process nucleic acid phosphodiester bond hydrolysis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 80198 71711 Ensembl ENSG00000172732 ENSMUSG00000024906 UniProt Q96NY9 Q91ZJ0 RefSeq (mRNA) NM_025128 NM_001350283 NM_027877 RefSeq (protein) NP_079404 NP_001337212 NP_082153 Location (UCSC) Chr 11: 65.86 – 65.87 Mb Chr 19: 5.53 – 5.54 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

In mammalian somatic cells, MUS81 and another structure specific DNA endonuclease, XPF (ERCC4), play overlapping and essential roles in completion of homologous recombination.^[8] The significant overlap in function between these enzymes is most likely related to processing joint molecules such as D-loops and nicked Holliday junctions.^[8]

Meiosis

MUS81 is a component of a minor chromosomal crossover (CO) pathway in the meiosis of budding yeast, plants and vertebrates.^[9] However, in the protozoan Tetrahymena thermophila, MUS81 appears to be part of an essential (if not the predominant) CO pathway.^[9] The MUS81 pathway also appears to be the predominant CO pathway in the fission yeast Schizosaccharomyces pombe.^[9]

A current model of meiotic recombination, initiated by a double-strand break or gap, followed by pairing with an homologous chromosome and strand invasion to initiate the recombinational repair process. Repair of the gap can lead to crossover (CO) or non-crossover (NCO) of the flanking regions. CO recombination is thought to occur by the Double Holliday Junction (DHJ) model, illustrated on the right, above. NCO recombinants are thought to occur primarily by the Synthesis Dependent Strand Annealing (SDSA) model, illustrated on the left, above. Most recombination events appear to be the SDSA type.

The relationship of the CO pathway to the overall process of meiotic recombination is illustrated in the accompanying diagram. Recombination during meiosis is often initiated by a DNA double-strand break (DSB). During recombination, sections of DNA at the 5' ends of the break are cut away in a process called resection. In the strand invasion step that follows, an overhanging 3' end of the broken DNA molecule "invades" the DNA of an homologous chromosome that is not broken forming a displacement loop (D-loop). After strand invasion, the further sequence of events may follow either of two main pathways, leading to a crossover (CO) or a non-crossover (NCO) recombinant (see Genetic recombination). The pathway leading to a CO involves a double Holliday junction (DHJ) intermediate. Holliday junctions need to be resolved for CO recombination to be completed.

MUS81-MMS4, in the budding yeast Saccharomyces cerevisiae, is a DNA structure-selective endonuclease that cleaves joint DNA molecules formed during homologous recombination in meiosis and mitosis.^[10] The MUS81-MMS4 endonuclease, although a minor resolvase for CO formation in S. cerevisiae, is crucial for limiting chromosome entanglements by suppressing multiple consecutive recombination events from initiating from the same DSB.^[11]

Mus81 deficient mice have significant meiotic defects including the failure to repair a subset of DSBs.^[12]

Interactions

MUS81 has been shown to interact with CHEK2.^[5]