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Gene Review

MUS81  -  Mus81p

Saccharomyces cerevisiae S288c

Synonyms: Crossover junction endonuclease MUS81, D9509.6, MMS and UV-sensitive protein 81, SLX3, YDR386W
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Disease relevance of MUS81

  • Previous work has demonstrated that two structure-specific nucleases, Rad1 and Mus81, protect cells from camptothecin toxicity [1].

High impact information on MUS81

  • Mus81 proteins in yeasts and humans appear to have many, but not all, of the expected properties of eukaryotic Holliday junction resolvases, with intriguing connections to DNA replication checkpoints [2].
  • We also present genetic data that indicate a novel role for Mms4-Mus81 in meiotic recombination [3].
  • Here, we identify a similar interaction involving double mutations affecting Sgs1 or Top3 and Mus81 or Mms4 [4].
  • However, the MUS81/MMS4 replication fork restart pathway did not affect growth of rrm3 cells [5].
  • Further, mus81 sgs1 synthetic lethality requires homologous recombination, as does suppression of mutant phenotypes by RusA expression [6].

Biological context of MUS81


Associations of MUS81 with chemical compounds


Other interactions of MUS81

  • These data support a model in which defects in lagging-strand replication are repaired by the Mus81 endonuclease or through a pathway dependent on Rad51 and Sgs1 [12].
  • These data indicate that the primary function of SGS1, but not MUS81, is downstream of RAD51 [12].
  • Cells lacking RNH202 showed synthetic growth defects when combined with either mus81 or sgs1 alone [12].
  • We suggest that the absence of Mlh2p allows some crossovers from the MSH4 pathway to traverse the MUS81-dependent pathway [13].
  • The gene MUS81 p6ethyl methansulfonate, UV sensitive) was identified as clone 81 in a two-hybrid screen using the Saccharomyces cerevisiae Rad54 protein as a bait [7].

Analytical, diagnostic and therapeutic context of MUS81


  1. Multiple endonucleases function to repair covalent topoisomerase I complexes in Saccharomyces cerevisiae. Deng, C., Brown, J.A., You, D., Brown, J.M. Genetics (2005) [Pubmed]
  2. The fuss about Mus81. Haber, J.E., Heyer, W.D. Cell (2001) [Pubmed]
  3. Functional overlap between Sgs1-Top3 and the Mms4-Mus81 endonuclease. Kaliraman, V., Mullen, J.R., Fricke, W.M., Bastin-Shanower, S.A., Brill, S.J. Genes Dev. (2001) [Pubmed]
  4. Alternate pathways involving Sgs1/Top3, Mus81/ Mms4, and Srs2 prevent formation of toxic recombination intermediates from single-stranded gaps created by DNA replication. Fabre, F., Chan, A., Heyer, W.D., Gangloff, S. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  5. Saccharomyces cerevisiae Rrm3p DNA helicase promotes genome integrity by preventing replication fork stalling: viability of rrm3 cells requires the intra-S-phase checkpoint and fork restart activities. Torres, J.Z., Schnakenberg, S.L., Zakian, V.A. Mol. Cell. Biol. (2004) [Pubmed]
  6. The mechanism of Mus81-Mms4 cleavage site selection distinguishes it from the homologous endonuclease Rad1-Rad10. Bastin-Shanower, S.A., Fricke, W.M., Mullen, J.R., Brill, S.J. Mol. Cell. Biol. (2003) [Pubmed]
  7. MUS81 encodes a novel helix-hairpin-helix protein involved in the response to UV- and methylation-induced DNA damage in Saccharomyces cerevisiae. Interthal, H., Heyer, W.D. Mol. Gen. Genet. (2000) [Pubmed]
  8. Contractions and expansions of CAG/CTG trinucleotide repeats occur during ectopic gene conversion in yeast, by a MUS81-independent mechanism. Richard, G.F., Cyncynatus, C., Dujon, B. J. Mol. Biol. (2003) [Pubmed]
  9. The role of AtMUS81 in DNA repair and its genetic interaction with the helicase AtRecQ4A. Hartung, F., Suer, S., Bergmann, T., Puchta, H. Nucleic Acids Res. (2006) [Pubmed]
  10. Damage tolerance protein Mus81 associates with the FHA1 domain of checkpoint kinase Cds1. Boddy, M.N., Lopez-Girona, A., Shanahan, P., Interthal, H., Heyer, W.D., Russell, P. Mol. Cell. Biol. (2000) [Pubmed]
  11. DNA repair by a Rad22-Mus81-dependent pathway that is independent of Rhp51. Doe, C.L., Osman, F., Dixon, J., Whitby, M.C. Nucleic Acids Res. (2004) [Pubmed]
  12. Roles of SGS1, MUS81, and RAD51 in the repair of lagging-strand replication defects in Saccharomyces cerevisiae. Ii, M., Brill, S.J. Curr. Genet. (2005) [Pubmed]
  13. A role for the MutL homologue MLH2 in controlling heteroduplex formation and in regulating between two different crossover pathways in budding yeast. Abdullah, M.F., Hoffmann, E.R., Cotton, V.E., Borts, R.H. Cytogenet. Genome Res. (2004) [Pubmed]
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