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

• MUS81 encodes a novel helix-hairpin-helix protein involved in the response to UV- and methylation-induced DNA damage in Saccharomyces cerevisiae [7].
• Deletion of MUS81 caused a recessive methyl methansulfonate- and UV-sensitive phenotype [7].
• Contractions and expansions of CAG/CTG trinucleotide repeats occur during ectopic gene conversion in yeast, by a MUS81-independent mechanism [8].
• Homologues of the MUS81 gene exist in the genomes of all eukaryotes, pointing to a conserved role of the protein [9].
• Mus81 has an endonuclease homology domain found in the XPF nucleotide excision repair protein [10].

Associations of MUS81 with chemical compounds

• Mus81 enables survival of deoxynucleotide triphosphate starvation, UV radiation, and DNA polymerase impairment [10].
• In contrast Mus81 has a key role in the Rad22-dependent (Rhp51-independent) repair of damage induced by camptothecin, hydroxyurea and methyl-methanesulfonate [11].

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

• A complex containing Mus81p and Rad54p was identified in immunoprecipitation experiments [7].

References