MUS81 encodes a novel helix-hairpin-helix protein involved in the response to UV- and methylation-induced DNA damage in Saccharomyces cerevisiae.
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. It encodes a novel protein with a predicted molecular mass of 72,316 (632 amino acids) and contains two helix-hairpin-helix motifs, which are found in many proteins involved in DNA metabolism in bacteria, yeast, and mammals. Mus81p also shares homology with motifs found in the XPF endonuclease superfamily. Deletion of MUS81 caused a recessive methyl methansulfonate- and UV-sensitive phenotype. However, mus81delta cells were not significantly more sensitive than wild-type to gamma-radiation or double-strand breaks induced by HO endonuclease. Double mutant analysis suggests that Rad54p and Mus81p act in one pathway for the repair of, or tolerance to, UV-induced DNA damage. A complex containing Mus81p and Rad54p was identified in immunoprecipitation experiments. Deletion of MUS81 virtually eliminated sporulation in one strain background and reduced sporulation and spore viability in another. Potential homologs of Mus81p have been identified in Schizosaccharomyces pombe, Caenorhabditis elegans and Arabidopsis thaliana. We hypothesize that Mus81p plays a role in the recognition and/or processing of certain types of DNA damage (caused by UV and MMS) during repair or tolerance processes involving the recombinational repair pathway.
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Institute of General Microbiology, University of Bern, Switzerland.
Heyer
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004249:DNA Damage; D004265:DNA Helicases; D019175:DNA Methylation; D017931:DNA Primers / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D004720:Endonucleases; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics*; D005800:Genes, Fungal; D005816:Genetic Complementation Test; D019077:Helix-Turn-Helix Motifs / Q000235:genetics; D008540:Meiosis; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques; D014466:Ultraviolet Rays
D017931:DNA Primers; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; C095888:xeroderma pigmentosum group F protein; D008741:Methyl Methanesulfonate; D004720:Endonucleases; C411624:MUS81 protein, S cerevisiae; C075468:RAD54 protein, S cerevisiae; D004265:DNA Helicases; D045643:DNA Repair Enzymes