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Gene Review

SEM1  -  proteasome regulatory particle lid subunit...

Saccharomyces cerevisiae S288c

Synonyms: 26S proteasome complex subunit SEM1, DSH1, DSS1, HOD1, YDR363W-A
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Disease relevance of SEM1

  • Deletion of SEM1 or genes encoding other nonessential 19S or 20S proteasome subunits also results in synthetic growth defects and hypersensitivity to genotoxins when combined with mutations in well-established DNA DSB repair genes [1].
  • Interaction between the product of the breast cancer susceptibility gene BRCA2 and DSS1, a protein functionally conserved from yeast to mammals [2].
  • Sem1p-specific antibody isolated from a phage display library was expressed intracellularily and targeted to either the cytosol or the nucleus of yeast cells [3].

High impact information on SEM1

  • This phenotype was abolished after reintroduction of either SEM1 or the mouse homologue Dss1 into the cells [4].
  • In diploid cells that normally do not form pseudohyphae (S288C background), deletion of SEM1 triggered pseudohyphal growth [4].
  • SEM1 is not an essential gene [4].
  • Apparent orthologues of the mammalian DSS1 gene were identified in the genome of the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae [2].
  • Localization of the Fab intrabody with or without the nuclear localization signal to the nucleus in Sem1p-dependent manner suggests that Sem1p mediates the nuclear transport of the intrabody without any targeting signal [3].

Biological context of SEM1

  • Human DSS1 associates with BRCA2, a tumour suppressor protein required for efficient recombinational DNA repair, but the biochemical function of DSS1 is not known [5].

Analytical, diagnostic and therapeutic context of SEM1

  • The 19 S RP was immunoprecipitated together with Sem1 by immunoprecipitation using hemagglutinin epitope-tagged Sem1 as bait [6].
  • Cell fractionation showed that Sem1p is mainly cytosolic but also associates with the microsomal fraction [4].
  • Yeast strains in which these DSS1-like genes were deleted showed a temperature-sensitive growth phenotype, which was analyzed by flow cytometry [2].
  • Yeast and mammalian two-hybrid assays showed that DSS1 can associate with BRCA2 in the region of amino acids 2472 to 2957 in the C terminus of the protein [2].


  1. Proteasome involvement in the repair of DNA double-strand breaks. Krogan, N.J., Lam, M.H., Fillingham, J., Keogh, M.C., Gebbia, M., Li, J., Datta, N., Cagney, G., Buratowski, S., Emili, A., Greenblatt, J.F. Mol. Cell (2004) [Pubmed]
  2. Interaction between the product of the breast cancer susceptibility gene BRCA2 and DSS1, a protein functionally conserved from yeast to mammals. Marston, N.J., Richards, W.J., Hughes, D., Bertwistle, D., Marshall, C.J., Ashworth, A. Mol. Cell. Biol. (1999) [Pubmed]
  3. Functional inactivation of the conserved Sem1p in yeast by intrabodies. Reinman, M., Jäntti, J., Alfthan, K., Keränen, S., Söderlund, H., Takkinen, K. Yeast (2003) [Pubmed]
  4. SEM1, a homologue of the split hand/split foot malformation candidate gene Dss1, regulates exocytosis and pseudohyphal differentiation in yeast. Jäntti, J., Lahdenranta, J., Olkkonen, V.M., Söderlund, H., Keränen, S. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  5. Fission yeast Dss1 associates with the proteasome and is required for efficient ubiquitin-dependent proteolysis. Jossé, L., Harley, M.E., Pires, I.M., Hughes, D.A. Biochem. J. (2006) [Pubmed]
  6. Sem1p is a novel subunit of the 26 S proteasome from Saccharomyces cerevisiae. Sone, T., Saeki, Y., Toh-e, A., Yokosawa, H. J. Biol. Chem. (2004) [Pubmed]
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