The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

MAD3  -  Mad3p

Saccharomyces cerevisiae S288c

Synonyms: J1341, Mitotic MAD3 protein, Spindle assembly checkpoint component MAD3, YJL013C
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

High impact information on MAD3

  • MAD1 and MAD2 act in a surveillance mechanism that mediates a metaphase delay in response to nonexchange chromosomes, whereas MAD3 acts as a crucial meiotic timer, mediating a prophase delay in every meiosis [1].
  • Mad2 and Mad3 coprecipitated with Cdc20 at all stages of the cell cycle [2].
  • In vivo, we observed an increased binding of Cdc20p to Mad3p and decreased binding to Hsl1p upon checkpoint activation [3].
  • We show that the two regions of homology between Mad3p and Bub1p are crucial for these interactions and identify loss of function mutations within each domain of Mad3p [4].
  • Negative-stain electron microscopy shows that Mad3 is an extended molecule ( approximately 200 A long), whereas Bub3 is globular [5].

Biological context of MAD3


Associations of MAD3 with chemical compounds

  • Accordingly, replacing with alanines five serine residues belonging to Polo kinase-dependent putative phosphorylation sites dramatically reduces Mad3 phosphorylation, suggesting that Mad3 is likely an in vivo target of Cdc5 [8].
  • In addition, the NH2-terminal portion (161 amino acids) of hBub1 shows a significant homology to yeast MAD3, a protein also known to be involved in the mitotic checkpoint response pathway [9].

Physical interactions of MAD3

  • The checkpoint proteins Mad2 and Mad3/BubR1 bind to Cdc20, although how they inhibit APC(Cdc20) is unclear [3].

Other interactions of MAD3

  • The bub1-A78V mutant is of particular interest because it produces a wild-type amount of protein that is mutated in the conserved but uncharacterized Mad3-like region of Bub1p [10].
  • In budding yeast, Mad1, Mad2, and Mad3 proteins are equally required for arrest in the presence of damage induced by antimicrotubule drugs or catastrophic loss of spindle structure [11].
  • Instead, these motifs are important for Mad3p function in the checkpoint and for binding to Cdc20p [3].

Analytical, diagnostic and therapeutic context of MAD3


  1. The roles of MAD1, MAD2 and MAD3 in meiotic progression and the segregation of nonexchange chromosomes. Cheslock, P.S., Kemp, B.J., Boumil, R.M., Dawson, D.S. Nat. Genet. (2005) [Pubmed]
  2. Budding yeast Cdc20: a target of the spindle checkpoint. Hwang, L.H., Lau, L.F., Smith, D.L., Mistrot, C.A., Hardwick, K.G., Hwang, E.S., Amon, A., Murray, A.W. Science (1998) [Pubmed]
  3. Mad3p, a pseudosubstrate inhibitor of APCCdc20 in the spindle assembly checkpoint. Burton, J.L., Solomon, M.J. Genes Dev. (2007) [Pubmed]
  4. MAD3 encodes a novel component of the spindle checkpoint which interacts with Bub3p, Cdc20p, and Mad2p. Hardwick, K.G., Johnston, R.C., Smith, D.L., Murray, A.W. J. Cell Biol. (2000) [Pubmed]
  5. Structural analysis of Bub3 interactions in the mitotic spindle checkpoint. Larsen, N.A., Al-Bassam, J., Wei, R.R., Harrison, S.C. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  6. Distinct chromosome segregation roles for spindle checkpoint proteins. Warren, C.D., Brady, D.M., Johnston, R.C., Hanna, J.S., Hardwick, K.G., Spencer, F.A. Mol. Biol. Cell (2002) [Pubmed]
  7. Fission yeast Mad3p is required for Mad2p to inhibit the anaphase-promoting complex and localizes to kinetochores in a Bub1p-, Bub3p-, and Mph1p-dependent manner. Millband, D.N., Hardwick, K.G. Mol. Cell. Biol. (2002) [Pubmed]
  8. Mad3/BubR1 phosphorylation during spindle checkpoint activation depends on both Polo and Aurora kinases in budding yeast. Rancati, G., Crispo, V., Lucchini, G., Piatti, S. Cell Cycle (2005) [Pubmed]
  9. Human Bub1: a putative spindle checkpoint kinase closely linked to cell proliferation. Ouyang, B., Lan, Z., Meadows, J., Pan, H., Fukasawa, K., Li, W., Dai, W. Cell Growth Differ. (1998) [Pubmed]
  10. The A78V mutation in the Mad3-like domain of Schizosaccharomyces pombe Bub1p perturbs nuclear accumulation and kinetochore targeting of Bub1p, Bub3p, and Mad3p and spindle assembly checkpoint function. Kadura, S., He, X., Vanoosthuyse, V., Hardwick, K.G., Sazer, S. Mol. Biol. Cell (2005) [Pubmed]
  11. Bipolar orientation of chromosomes in Saccharomyces cerevisiae is monitored by Mad1 and Mad2, but not by Mad3. Lee, M.S., Spencer, F.A. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
WikiGenes - Universities