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MUS81
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Main page Crossover junction endonuclease MUS81 is an

MUS81
Contents enzyme that in humans is encoded by the MUS81
Current events gene.[5][6][7] Available structures
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About Wikipedia
In mammalian somatic cells, MUS81 and another
structure specific DNA endonuclease, XPF (ERCC4), List of PDB id codes
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Donate play overlapping and essential roles in completion of 2MC3, 4P0P, 4P0Q, 4P0R, 4P0S
homologous recombination.[8] The significant overlap in
Contribute Identifiers
function between these enzymes is most likely related to
Help Aliases MUS81, SLX3, MUS81 structure-specific
processing joint molecules such as D-loops and nicked
Learn to edit endonuclease subunit
Holliday junctions.[8]
Community portal External OMIM: 606591 MGI: 1918961 HomoloGene: 5725
Recent changes IDs GeneCards: MUS81
Contents [hide]
Upload file Gene location (Human)
1 Meiosis
Tools 2 Interactions
What links here 3 References
Related changes 4 Further reading
Special pages
Permanent link
Page information Meiosis [edit]
Cite this page Chr. Chromosome 11 (human)[1]
Wikidata item
MUS81 is a component of a minor chromosomal
crossover (CO) pathway in the meiosis of budding
Print/export yeast, plants and vertebrates.[9] However, in the
Download as PDF protozoan Tetrahymena thermophila, MUS81 appears to Band 11q13.1 Start 65,857,126 bp[1]
be part of an essential (if not the predominant) CO
Languages End 65,867,653 bp[1]
pathway.[9] The MUS81 pathway also appears to be the
Татарча/tatarça Gene location (Mouse)
predominant CO pathway in the fission yeast
Українська
Edit links Schizosaccharomyces pombe.[9]
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 Chr. Chromosome 19 (mouse)[2]
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
Band 19|19 A Start 5,482,345 bp[2]
an homologous chromosome that is not broken forming
End 5,488,402 bp[2]
a displacement loop (D-loop). After strand invasion, the
further sequence of events may follow either of two main RNA expression pattern
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 More reference expression data
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 Gene ontology
multiple consecutive recombination events from initiating Molecular • DNA binding
from the same DSB.[11] function • nuclease activity
Mus81 deficient mice have significant meiotic defects • endonuclease activity
• GO:0001948 protein binding
including the failure to repair a subset of DSBs.[12] • 3'-flap endonuclease activity
• metal ion binding
Interactions [edit] • hydrolase activity
• endodeoxyribonuclease activity
MUS81 has been shown to interact with CHEK2.[5] • crossover junction
endodeoxyribonuclease activity
References [edit]
Cellular • nucleoplasm
1. ^a b c GRCh38: Ensembl release 89: component • cell nucleus
ENSG00000172732 - Ensembl, May 2017 • nucleolus
2. ^ a b c GRCm38: Ensembl release 89: • Holliday junction resolvase complex
ENSMUSG00000024906 - Ensembl, May 2017 Biological • DNA recombination
3. ^ "Human PubMed Reference:" . National Center for process • interstrand cross-link repair
Biotechnology Information, U.S. National Library of • DNA catabolic process, endonucleolytic
Medicine. • cellular response to DNA damage
4. ^ "Mouse PubMed Reference:" . National Center for stimulus
Biotechnology Information, U.S. National Library of • response to intra-S DNA damage
Medicine. checkpoint signaling
5. ^ a b Chen XB, Melchionna R, Denis CM, Gaillard PH, • DNA repair
• resolution of meiotic recombination
Blasina A, Van de Weyer I, Boddy MN, Russell P,
intermediates
Vialard J, McGowan CH (Nov 2001). "Human Mus81- • double-strand break repair via break-
associated endonuclease cleaves Holliday junctions in induced replication
vitro". Molecular Cell. 8 (5): 1117–27. • mitotic G2 DNA damage checkpoint
doi:10.1016/S1097-2765(01)00375-6 . • replication fork processing
PMID 11741546 . • intra-S DNA damage checkpoint
6. ^ Constantinou A, Chen XB, McGowan CH, West SC • DNA metabolic process
(Oct 2002). "Holliday junction resolution in human • nucleic acid phosphodiester bond
cells: two junction endonucleases with distinct hydrolysis
substrate specificities" . The EMBO Journal. 21 (20): Sources:Amigo / QuickGO
5577–85. doi:10.1093/emboj/cdf554 .
PMC 129086 . PMID 12374758 .
7. ^ "Entrez Gene: MUS81 MUS81 endonuclease
homolog (S. cerevisiae)" . Orthologs
8. ^ a b Kikuchi K, Narita T, Pham VT, Iijima J, Hirota K, Species Human Mouse
Keka IS, Mohiuddin, Okawa K, Hori T, Fukagawa T, Entrez
Essers J, Kanaar R, Whitby MC, Sugasawa K, 80198 71711
Taniguchi Y, Kitagawa K, Takeda S (2013). "Structure- Ensembl
specific endonucleases xpf and mus81 play ENSG00000172732 ENSMUSG00000024906
overlapping but essential roles in DNA repair by
UniProt
homologous recombination" . Cancer Res. 73 (14): Q96NY9 Q91ZJ0
4362–71. doi:10.1158/0008-5472.CAN-12-3154 .
PMC 3718858 . PMID 23576554 . RefSeq
9. ^ a b c Lukaszewicz A, Howard-Till RA, Loidl J (2013). (mRNA) NM_025128 NM_027877
NM_001350283
"Mus81 nuclease and Sgs1 helicase are essential for
meiotic recombination in a protist lacking a RefSeq
synaptonemal complex" . Nucleic Acids Res. 41 (protein) NP_079404 NP_082153
NP_001337212
(20): 9296–309. doi:10.1093/nar/gkt703 .
PMC 3814389 . PMID 23935123 . Location Chr 11: 65.86 – Chr 19: 5.48 – 5.49 Mb
10. ^ Mukherjee S, Wright WD, Ehmsen KT, Heyer WD (UCSC) 65.87 Mb
(2014). "The Mus81-Mms4 structure-selective PubMed [3] [4]
endonuclease requires nicked DNA junctions to search
undergo conformational changes and bend its DNA Wikidata
substrates for cleavage" . Nucleic Acids Res. 42 View/Edit Human View/Edit Mouse
(10): 6511–22. doi:10.1093/nar/gku265 .
PMC 4041439 . PMID 24744239 .
11. ^ 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 .
 PMC 4199502 . PMID 25329811 .
12. ^ 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 .

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.
Further reading [edit]
Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic
mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8 . PMID 8125298 .
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and
characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56.
doi:10.1016/S0378-1119(97)00411-3 . PMID 9373149 .
Boddy MN, Lopez-Girona A, Shanahan P, Interthal H, Heyer WD, Russell P (Dec 2000). "Damage tolerance protein
Mus81 associates with the FHA1 domain of checkpoint kinase Cds1" . Molecular and Cellular Biology. 20 (23):
8758–66. doi:10.1128/MCB.20.23.8758-8766.2000 . PMC 86503 . PMID 11073977 .
Oğrünç M, Sancar A (Jun 2003). "Identification and characterization of human MUS81-MMS4 structure-specific
endonuclease" . The Journal of Biological Chemistry. 278 (24): 21715–20. doi:10.1074/jbc.M302484200 .
PMID 12686547 .
Ciccia A, Constantinou A, West SC (Jul 2003). "Identification and characterization of the human mus81-eme1
endonuclease" . The Journal of Biological Chemistry. 278 (27): 25172–8. doi:10.1074/jbc.M302882200 .
PMID 12721304 .
Blais V, Gao H, Elwell CA, Boddy MN, Gaillard PH, Russell P, McGowan CH (Feb 2004). "RNA interference inhibition
of Mus81 reduces mitotic recombination in human cells" . Molecular Biology of the Cell. 15 (2): 552–62.
doi:10.1091/mbc.E03-08-0580 . PMC 329235 . PMID 14617801 .
Gao H, Chen XB, McGowan CH (Dec 2003). "Mus81 endonuclease localizes to nucleoli and to regions of DNA
damage in human S-phase cells" . Molecular Biology of the Cell. 14 (12): 4826–34. doi:10.1091/mbc.E03-05-0276 .
PMC 284787 . PMID 14638871 .
Zhang R, Sengupta S, Yang Q, Linke SP, Yanaihara N, Bradsher J, Blais V, McGowan CH, Harris CC (Apr 2005).
"BLM helicase facilitates Mus81 endonuclease activity in human cells" . Cancer Research. 65 (7): 2526–31.
doi:10.1158/0008-5472.CAN-04-2421 . PMID 15805243 .
 Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-
Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL,
Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute
J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct
2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8.
doi:10.1038/nature04209 . PMID 16189514 . S2CID 4427026 .
Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K,
Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T,
Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai
K, Isogai T, Sugano S (Jan 2006). "Diversification of transcriptional modulation: large-scale identification and
characterization of putative alternative promoters of human genes" . Genome Research. 16 (1): 55–65.
doi:10.1101/gr.4039406 . PMC 1356129 . PMID 16344560 .
Hiyama T, Katsura M, Yoshihara T, Ishida M, Kinomura A, Tonda T, Asahara T, Miyagawa K (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. 34 (3): 880–92. doi:10.1093/nar/gkj495 .
PMC 1360746 . PMID 16456034 .
Ii M, Ii T, Brill SJ (Dec 2007). "Mus81 functions in the quality control of replication forks at the rDNA and is involved in
the maintenance of rDNA repeat number in Saccharomyces cerevisiae" . Mutation Research. 625 (1–2): 1–19.
doi:10.1016/j.mrfmmm.2007.04.007 . PMC 2100401 . PMID 17555773 .
Nomura Y, Adachi N, Koyama H (Oct 2007). "Human Mus81 and FANCB independently contribute to repair of DNA
damage during replication". Genes to Cells. 12 (10): 1111–22. doi:10.1111/j.1365-2443.2007.01124.x .
PMID 17903171 . S2CID 33382415 .

Categories: Genes on human chromosome 11

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