Recombinant Human Crossover junction endonuclease MUS81 (MUS81)

1. Replication fork progression in BRCA2-deficient cells requires MUS81. MUS81 nucleolytic activity is required to activate compensatory DNA synthesis during mitosis and to resolve mitotic interlinks, thus facilitating chromosome segregation. PMID: 28714477
2. Using RNAi or FA-P cells complemented with SLX4 mutants that abrogate interaction with MUS81 or SLX1, we show that SLX4 cooperates with MUS81 to introduce DSBs after replication stress but also counteracts pathological targeting of demised forks by GEN1. PMID: 28290553
3. The results showed that MUS81 modulates MCM2 levels as well as homologous recombination (HR) activity. Moreover, downregulation of MUS81 increased the sensitivity of epithelial ovarian cancer (EOC)cells to olaparib by inducing S phase arrest and promoting apoptosis through activation of MCM2. MUS81 may be a potential novel therapeutic target for EOC. PMID: 29393493
4. Mus81 knockdown improves the chemosensitivity of colon cancer cells by inducing S phase arrest and promoting apoptosis through activating CHK1 pathway PMID: 28291626
5. Low EZH2 or MUS81 expression levels predict chemoresistance. PMID: 29035360
6. RECQ5 removes RAD51 filaments stabilizing stalled replication forks at common fragile sites and hence facilitates CFS cleavage by MUS81-EME1. PMID: 28575661
7. The mitotic DNA synthesis is RAD52 dependent, and RAD52 is required for the timely recruitment of MUS81 and POLD3 to common fragile sites in early mitosis. PMID: 27984745
8. Data suggest that dimeric GEN1 binds with high affinity/selectivity to Holliday junctions, introducing two symmetrical hydrolytic cleavages of phosphodiester backbone; at present, less is known about SLX1-SLX4-MUS81-EME1 resolving enzyme complex. (GEN1 = Holliday junction 5' flap endonuclease; SLX = structure-specific endonuclease subunit; MUS81 = MUS81 endonuclease; EME1 = essential meiotic endonuclease 1) [REVIEW] PMID: 27990631
9. down-regulation of MUS81 expression in ovarian cancer cells inhibited cell proliferation and colony formation ability, and influenced cell cycle progression PMID: 27255997
10. SLX4-SLX1 Protein-independent Down-regulation of MUS81-EME1 Protein by HIV-1 Viral Protein R (Vpr). PMID: 27354282
11. Mus81 sumoylation is important for normal mitotic chromosome congression. PMID: 28318385
12. Data suggest that the ATM/Chk2 may promote the repair of DNA damage caused by cisplatin by sustaining methyl methanesulfonate and ultraviolet-sensitive gene clone 81, and the double-strand breaks generated by methyl methanesulfonate and ultraviolet-sensitive gene clone 81 may activate the ATM/Chk2 pathway. PMID: 28347251
13. Avoiding damage formation through invalidation of Mus81-Eme2 and Mre11, or preventing damage signaling by turning off the ATM pathway, suppresses the replication phenotypes of Chk1-deficient cells. PMID: 26804904
14. Mus81 knockdown improves the chemosensitivity of HCC cells by inducing S-phase arrest and promoting apoptosis through CHK1 pathway, suggesting Mus81 as a novel therapeutic target for HCC. PMID: 26714930
15. Mus81 regulates the rate of DNA replication during normal growth by promoting replication fork progression while reducing the frequency of replication initiation events. PMID: 25879486
16. Identification and characterization of MUS81 point mutations that abolish interaction with the SLX4 scaffold protein.MUS81 function in DNA interstrand crosslinks repair requires interaction with SLX4. PMID: 25224045
17. The data highlight the importance of Mus81 and Blm in DNA double-strand repair pathways, fertility, development and cancer. PMID: 24858046
18. Authors confirmed that HIV-1 Vpr induces degradation of Mus81 although, surprisingly, degradation is independent and genetically separable from Vprs ability to induce G2 arrest. PMID: 25618414
19. Results define distinct and temporal roles for MUS81-EME1 and MUS81-EME2 in the maintenance of genome stability. PMID: 24813886
20. Our findings reveal a novel RAD52/MUS81-dependent mechanism that promotes cell viability and genome integrity in checkpoint-deficient cells, and disclose the involvement of MUS81 to multiple processes after replication stress PMID: 24204313
21. While Mus81-Eme1 shares several common features with members of the 5' flap nuclease family, the combined structural, biochemical, and biophysical analyses explain why Mus81-Eme1 preferentially cleaves 3' flap DNA substrates with 5' nicked ends. PMID: 24733841
22. In vivo HJ resolution depends on both SLX4-associated MUS81-EME1 and SLX1, suggesting that they are acting in concert in the context of SLX4. PMID: 24080495
23. The presence of a 5' phosphate terminus at nicks and gaps rendered DNA significantly less susceptible to the cleavage by MUS81-EME2 than its absence. PMID: 24692662
24. This study identified a winged helix domain within the N-terminal region of human MUS81 that binds DNA, increases the activity of MUS81-EME1/EME2 complexes and influences the incision position of MUS81-EME2 but not MUS81-EME1 complexes on synthetic forks, 3' flaps and nicked Holliday junctions. PMID: 23982516
25. Data show that three structure-selective endonucleases, SLX1-SLX4, MUS81-EME1, and GEN1, define two pathways of Holliday junctions (HJs) resolution in HeLa cells. PMID: 24076221
26. the DNA structure-specific nuclease MUS81-EME1 localizes to CFS loci in early mitotic cells, and promotes the cytological appearance of characteristic gaps or breaks observed at CFSs in metaphase chromosomes. PMID: 23811685
27. FBH1 helicase activity is required to eliminate cells with excessive replication stress through the generation of MUS81-induced DNA double-strand breaks. PMID: 23361013
28. we demonstrate that 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. PMID: 22410776
29. Data show that Mus81/Eme1-dependent DNA damage--rather than a global increase in replication-fork stalling--is the cause of incomplete replication in Chk1-deficient cells. PMID: 21858151
30. Mus81 cleaves stalled replication forks, which allows dissipation of the excessive supercoiling resulting from Top1 inhibition, spontaneous reversal of Top1cc, and replication fork progression. PMID: 22123861
31. Results demonstrate a novel role of Wee1 in controlling Mus81-Eme1 and DNA replication in human cells. PMID: 21859861
32. Mus81 is a novel prognostic marker for colorectal carcinoma PMID: 21175991
33. Mus81 down-regulation correlated significantly to invasion depth (p = 0.015) and poorly-differentiated type (p = 0.016) of gastric cancer. PMID: 21187482
34. Mus81-associated endonuclease may play a more direct role in replication fork collapse by catalysing the cleavage of stalled fork structures. PMID: 12374758
35. hMUS81.hMMS4 complex is a structure-specific nuclease that is capable of resolving fork structure [hMMS4] PMID: 12686547
36. Mus81 binds to a homolog of fission yeast Eme1 in vitro and in vivo and Mus81-Eme1 resolves Holliday junctions in vivo. PMID: 14617801
37. Mus81 is required to repair problems that arise most frequently in the highly repetitive nucleolar DNA. PMID: 14638871
38. Data suggest a new function of BLM in cooperating with Mus81 during processing and restoration of stalled replication forks. PMID: 15805243
39. Mus81 deficiency affects cell cycle progression and promotes DNA rereplication. PMID: 16456034
40. Pulsed-field gel electrophoresis of the mus81Delta mutant revealed an expansion of the rDNA locus depending on RAD52, in addition to fragmentation of Chr XII in the sgs1Deltamus81(ts) mutant at permissive temperature. PMID: 17555773
41. Mus81 and FANCB have different roles in repair of DNA damage during replication in human cells PMID: 17903171
42. Data suggest that Mus81 suppresses chromosomal instability by converting potentially detrimental replication-associated DNA structures into intermediates that are more amenable to DNA repair. PMID: 17934473
43. BLM helicase and Mus81 are required to induce transient double-stranded DNA breaks in response to DNA replication stress. PMID: 18054789
44. Mus81-Eme1 can ensure coordinate, bilateral cleavage of Holliday junction-like structures. PMID: 18310322
45. the crystal structure of the Mus81-Eme1 complex PMID: 18413719
46. Mutations and abnormal expression of MUS81 gene in the LSCC tissues were observed. PMID: 18841572
47. WRN is required to avoid accumulation of double-strand breaks and fork collapse after replication perturbation, and that prompt MUS81-dependent generation of DSBs is instrumental for recovery from hydroxyurea-mediated replication arrest. PMID: 18852298
48. results demonstrate a link between branch migration activity of hRad54 and structure-specific endonuclease activity of hMus81-Eme1, suggesting that the Rad54 and Mus81-Eme1 proteins may cooperate in the processing of Holliday junction-like intermediates PMID: 19017809
49. MUS81 is involved in the maintenance of ALT (alternative lengthening of telomeres) cell survival at least in part by homologous recombination of telomeres. PMID: 19363487

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HGNC: 29814

OMIM: 606591

KEGG: hsa:80198

STRING: 9606.ENSP00000307853

UniGene: Hs.288798