MUS81

MUS81 structure-specific endonuclease subunit
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols MUS81 ; SLX3
External IDs OMIM: 606591 MGI: 1918961 HomoloGene: 5725 GeneCards: MUS81 Gene
EC number 3.1.22.-
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 80198 71711
Ensembl ENSG00000172732 ENSMUSG00000024906
UniProt Q96NY9 Q91ZJ0
RefSeq (mRNA) NM_025128 NM_027877
RefSeq (protein) NP_079404 NP_082153
Location (UCSC) Chr 11:
65.86 – 65.87 Mb		 Chr 19:
5.48 – 5.49 Mb
PubMed search

Crossover junction endonuclease MUS81 is an enzyme that in humans is encoded by the MUS81 gene.[1][2][3]

In mammalian somatic cells, MUS81 and another structure specific DNA endonuclease, XPF (ERCC4), play overlapping and essential roles in completion of homologous recombination.[4] The significant overlap in function between these enzymes is most likely related to processing joint molecules such as D-loops and nicked Holliday junctions.[4]

Meiosis

MUS81 is a component of a minor chromosomal crossover (CO) pathway in the meiosis of budding yeast, plants and vertebrates.[5] However in the protozoan Tetrahymena thermophila, MUS81 appears to be part of an essential (if not the predominant) CO pathway.[5] The MUS81 pathway also appears to be the predominant CO pathway in the fission yeast Schizosaccharomyces pombe.[5]

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.

MU81-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.[6] 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.[7]

Mus81 deficient mice have significant meiotic defects including the failure to repair a subset of DSBs.[8]

Interactions

MUS81 has been shown to interact with CHEK2.[1]

References

  1. 1 2 Chen XB, Melchionna R, Denis CM, Gaillard PH, Blasina A, Van de Weyer I, Boddy MN, Russell P, Vialard J, McGowan CH (Nov 2001). "Human Mus81-associated endonuclease cleaves Holliday junctions in vitro". Molecular Cell 8 (5): 1117–27. doi:10.1016/S1097-2765(01)00375-6. PMID 11741546.
  2. ↑ Constantinou A, Chen XB, McGowan CH, West SC (Oct 2002). "Holliday junction resolution in human cells: two junction endonucleases with distinct substrate specificities". The EMBO Journal 21 (20): 5577–85. doi:10.1093/emboj/cdf554. PMC 129086. PMID 12374758.
  3. ↑ "Entrez Gene: MUS81 MUS81 endonuclease homolog (S. cerevisiae)".
  4. 1 2 Kikuchi K, Narita T, Pham VT, Iijima J, Hirota K, Keka IS, Mohiuddin, Okawa K, Hori T, Fukagawa T, Essers J, Kanaar R, Whitby MC, Sugasawa K, Taniguchi Y, Kitagawa K, Takeda S (2013). "Structure-specific endonucleases xpf and mus81 play overlapping but essential roles in DNA repair by homologous recombination". Cancer Res. 73 (14): 4362–71. doi:10.1158/0008-5472.CAN-12-3154. PMC 3718858. PMID 23576554.
  5. 1 2 3 Lukaszewicz A, Howard-Till RA, Loidl J (2013). "Mus81 nuclease and Sgs1 helicase are essential for meiotic recombination in a protist lacking a synaptonemal complex". Nucleic Acids Res. 41 (20): 9296–309. doi:10.1093/nar/gkt703. PMC 3814389. PMID 23935123.
  6. ↑ Mukherjee S, Wright WD, Ehmsen KT, Heyer WD (2014). "The Mus81-Mms4 structure-selective endonuclease requires nicked DNA junctions to undergo conformational changes and bend its DNA substrates for cleavage". Nucleic Acids Res. 42 (10): 6511–22. doi:10.1093/nar/gku265. PMC 4041439. PMID 24744239.
  7. ↑ Oke A, Anderson CM, Yam P, Fung JC (2014). "Controlling meiotic recombinational repair - specifying the roles of ZMMs, Sgs1 and Mus81/Mms4 in crossover formation". PLoS Genet. 10 (10): e1004690. doi:10.1371/journal.pgen.1004690. PMC 4199502. PMID 25329811.
  8. ↑ Holloway JK, Booth J, Edelmann W, McGowan CH, Cohen PE (2008). "MUS81 generates a subset of MLH1-MLH3-independent crossovers in mammalian meiosis". PLoS Genet. 4 (9): e1000186. doi:10.1371/journal.pgen.1000186. PMC 2525838. PMID 18787696.

Further reading

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