Gene Symbol: MAD3
Description: Mad3p
Alias: Mad3p
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Hwang L, Lau L, Smith D, Mistrot C, Hardwick K, Hwang E, et al. Budding yeast Cdc20: a target of the spindle checkpoint. Science. 1998;279:1041-4 pubmed
    ..In the two-hybrid system, three proteins that are components of the checkpoint, Mad1, Mad2, and Mad3, were shown to interact with Cdc20, a protein required for exit from mitosis...
  2. Hardwick K, Johnston R, Smith D, Murray A. MAD3 encodes a novel component of the spindle checkpoint which interacts with Bub3p, Cdc20p, and Mad2p. J Cell Biol. 2000;148:871-82 pubmed
    ..Sequence analysis reveals two regions of Mad3p that are 46 and 47% identical to sequences in the NH(2)-terminal region of the budding yeast Bub1 protein kinase...
  3. Larsen N, Al Bassam J, Wei R, Harrison S. Structural analysis of Bub3 interactions in the mitotic spindle checkpoint. Proc Natl Acad Sci U S A. 2007;104:1201-6 pubmed
    The Mad3/BubR1, Mad2, Bub1, and Bub3 proteins are gatekeepers for the transition from metaphase to anaphase. Mad3 from Saccharomyces cerevisiae has homology to Bub1 but lacks a corresponding C-terminal kinase domain...
  4. Hardwick K, Li R, Mistrot C, Chen R, Dann P, Rudner A, et al. Lesions in many different spindle components activate the spindle checkpoint in the budding yeast Saccharomyces cerevisiae. Genetics. 1999;152:509-18 pubmed
    ..the checkpoint can detect by examining the interaction of mutations that compromise the checkpoint (mad1, mad2, and mad3) with those that damage various structural components of the spindle...
  5. Wilson D, Cerna D, Chew E. The 1.1-angstrom structure of the spindle checkpoint protein Bub3p reveals functional regions. J Biol Chem. 2005;280:13944-51 pubmed
    ..It is known to function by co-localizing at least two other proteins, Mad3p and the protein kinase Bub1p, to the kinetochore of chromosomes that are not properly attached to mitotic spindles,..
  6. Poddar A, Stukenberg P, Burke D. Two complexes of spindle checkpoint proteins containing Cdc20 and Mad2 assemble during mitosis independently of the kinetochore in Saccharomyces cerevisiae. Eukaryot Cell. 2005;4:867-78 pubmed
    Favored models of spindle checkpoint signaling propose that two inhibitory complexes (Mad2-Cdc20 and Mad2-Mad3-Bub3-Cdc20) must be assembled at kinetochores in order to inhibit mitosis...
  7. Matson D, Demirel P, Stukenberg P, Burke D. A conserved role for COMA/CENP-H/I/N kinetochore proteins in the spindle checkpoint. Genes Dev. 2012;26:542-7 pubmed publisher
    ..We propose a model to explain the differential response of human cells to nocodazole and paclitaxel...
  8. Lee M, Spencer F. Bipolar orientation of chromosomes in Saccharomyces cerevisiae is monitored by Mad1 and Mad2, but not by Mad3. Proc Natl Acad Sci U S A. 2004;101:10655-60 pubmed
    ..In budding yeast, Mad1, Mad2, and Mad3 proteins are equally required for arrest in the presence of damage induced by antimicrotubule drugs or catastrophic ..
  9. Cheslock P, Kemp B, Boumil R, Dawson D. The roles of MAD1, MAD2 and MAD3 in meiotic progression and the segregation of nonexchange chromosomes. Nat Genet. 2005;37:756-60 pubmed
    ..This function of Mad3p could also be carried out by human BubR1...

More Information


  1. Myung K, Smith S, Kolodner R. Mitotic checkpoint function in the formation of gross chromosomal rearrangements in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2004;101:15980-5 pubmed
    ..These data suggest that functional mitotic checkpoints can play a role in the formation of genome rearrangements. ..
  2. Wang R, Burton J, Solomon M. Transcriptional and post-transcriptional regulation of Cdc20 during the spindle assembly checkpoint in S. cerevisiae. Cell Signal. 2017;33:41-48 pubmed publisher
    ..These findings contribute to our understanding of how the inhibition of APCCdc20 activity and enhanced Cdc20 degradation are required for proper spindle checkpoint arrest. ..
  3. Schibler A, Koutelou E, Tomida J, Wilson Pham M, Wang L, Lu Y, et al. Histone H3K4 methylation regulates deactivation of the spindle assembly checkpoint through direct binding of Mad2. Genes Dev. 2016;30:1187-97 pubmed publisher
    ..Collectively, our data indicate that interactions between Mad2 and H3K4 regulate resolution of the SAC by limiting closed Mad2 availability for Cdc20 inhibition. ..
  4. Lau D, Murray A. Mad2 and Mad3 cooperate to arrest budding yeast in mitosis. Curr Biol. 2012;22:180-90 pubmed publisher
    ..We found that expression of a Mad2-Mad3 protein fusion or noncovalently linked Mad2 and Mad3, but not the overexpression of the two separate proteins, ..
  5. Yong Gonzalez V, Wang B, Butylin P, Ouspenski I, Strunnikov A. Condensin function at centromere chromatin facilitates proper kinetochore tension and ensures correct mitotic segregation of sister chromatids. Genes Cells. 2007;12:1075-90 pubmed
    ..These findings show that, in addition to its essential role in rDNA segregation, condensin mediates segregation of the whole genome by maintaining the centromere structure in Saccharomyces cerevisiae. ..
  6. Rancati G, Crispo V, Lucchini G, Piatti S. Mad3/BubR1 phosphorylation during spindle checkpoint activation depends on both Polo and Aurora kinases in budding yeast. Cell Cycle. 2005;4:972-80 pubmed
    ..quot;wait anaphase" signal transmitted by the SAC, which involves the evolutionarily conserved Mad1, Mad2, Mad3/BubR1, Bub1, Bub3 and Mps1 proteins, and inhibits the activity of the ubiquitin ligase Cdc20/APC, that promotes ..
  7. Rudner A, Hardwick K, Murray A. Cdc28 activates exit from mitosis in budding yeast. J Cell Biol. 2000;149:1361-76 pubmed
    ..The defects of CDC28-VF suggest that Cdc28 activity is required to induce the metaphase to anaphase transition and initiate the transition from anaphase to G1 in budding yeast...
  8. Andrews C, Vas A, Meier B, Giménez Abián J, Diaz Martinez L, Green J, et al. A mitotic topoisomerase II checkpoint in budding yeast is required for genome stability but acts independently of Pds1/securin. Genes Dev. 2006;20:1162-74 pubmed
    ..Thus, compromised Topo II function activates a yeast checkpoint system that operates by a novel mechanism. ..
  9. King E, van der Sar S, Hardwick K. Mad3 KEN boxes mediate both Cdc20 and Mad3 turnover, and are critical for the spindle checkpoint. PLoS ONE. 2007;2:e342 pubmed
    ..The mitotic checkpoint complex (MCC, consisting of Mad3p, Mad2p, Bub3p and Cdc20p in budding yeast) is a potent APC/C inhibitor...
  10. King E, Rachidi N, Morrice N, Hardwick K, Stark M. Ipl1p-dependent phosphorylation of Mad3p is required for the spindle checkpoint response to lack of tension at kinetochores. Genes Dev. 2007;21:1163-8 pubmed
    ..Here we identify residues in the checkpoint protein Mad3p that are phosphorylated by Ipl1p...
  11. Chiroli E, Rancati G, Catusi I, Lucchini G, Piatti S. Cdc14 inhibition by the spindle assembly checkpoint prevents unscheduled centrosome separation in budding yeast. Mol Biol Cell. 2009;20:2626-37 pubmed publisher
    ..We propose that, besides inhibiting sister chromatid separation, the SAC preserves the accurate transmission of chromosomes also by preventing SPBs to migrate far apart until the conditions to assemble a bipolar spindle are satisfied. ..
  12. Newnham L, Jordan P, Rockmill B, Roeder G, Hoffmann E. The synaptonemal complex protein, Zip1, promotes the segregation of nonexchange chromosomes at meiosis I. Proc Natl Acad Sci U S A. 2010;107:781-5 pubmed publisher
    ..A mutation in the MAD3 gene, which encodes a component of the spindle checkpoint, also increases the nondisjunction of NECs...
  13. Mariani L, Chiroli E, Nezi L, Muller H, Piatti S, Musacchio A, et al. Role of the Mad2 dimerization interface in the spindle assembly checkpoint independent of kinetochores. Curr Biol. 2012;22:1900-8 pubmed publisher
    ..Surprisingly, downstream of kinetochores the surface does not mediate Mad2 dimerization. Instead, our results are consistent with a role of Mad3 as the main interactor of Mad2 via the dimerization surface.
  14. Farr K, Hoyt M. Bub1p kinase activates the Saccharomyces cerevisiae spindle assembly checkpoint. Mol Cell Biol. 1998;18:2738-47 pubmed
    ..delay was dependent upon the functions of the other checkpoint genes, including BUB2 and BUB3 and MAD1, MAD2, and MAD3. We found that the mitotic delay caused by BUB1-5 or MPS1 overexpression was interdependent upon the function of ..
  15. Burton J, Solomon M. Mad3p, a pseudosubstrate inhibitor of APCCdc20 in the spindle assembly checkpoint. Genes Dev. 2007;21:655-67 pubmed
    ..Although such motifs usually mediate APC-substrate recognition and ubiquitination, they have no apparent role in Mad3p turnover in Saccharomyces cerevisiae...
  16. Fraschini R, Beretta A, Sironi L, Musacchio A, Lucchini G, Piatti S. Bub3 interaction with Mad2, Mad3 and Cdc20 is mediated by WD40 repeats and does not require intact kinetochores. EMBO J. 2001;20:6648-59 pubmed
    The kinetochore checkpoint pathway, involving the Mad1, Mad2, Mad3, Bub1, Bub3 and Mps1 proteins, prevents anaphase entry and mitotic exit by inhibiting the anaphase promoting complex activator Cdc20 in response to monopolar attachment of ..
  17. Alexandru G, Zachariae W, Schleiffer A, Nasmyth K. Sister chromatid separation and chromosome re-duplication are regulated by different mechanisms in response to spindle damage. EMBO J. 1999;18:2707-21 pubmed
    ..Blocking APCCdh1-mediated Clb2 proteolysis and chromosome re-duplication does not require Mad2 but a different protein, Bub2. Our data imply that Mad1, Mad2, Mad3 and Bub1 regulate APCCdc20, whereas Bub2 regulates APCCdh1.
  18. Bogomolnaya L, Pathak R, Guo J, Cham R, Aramayo R, Polymenis M. Hym1p affects cell cycle progression in Saccharomyces cerevisiae. Curr Genet. 2004;46:183-92 pubmed
    ..Our overall data suggest that Hym1p has a regulatory role in cell cycle progression. ..
  19. Herrero E, Thorpe P. Synergistic Control of Kinetochore Protein Levels by Psh1 and Ubr2. PLoS Genet. 2016;12:e1005855 pubmed publisher
    ..Together these data show that Psh1 and Ubr2 synergistically control the amount of proteins at the kinetochore. ..
  20. Mora Santos M, Hervás Aguilar A, Sewart K, Lancaster T, Meadows J, Millar J. Bub3-Bub1 Binding to Spc7/KNL1 Toggles the Spindle Checkpoint Switch by Licensing the Interaction of Bub1 with Mad1-Mad2. Curr Biol. 2016;26:2642-2650 pubmed publisher
    ..Spindle checkpoint proteins, including Mad1, Mad2, Mad3 (BubR1), Bub1, Bub3, and Mph1 (Mps1), are recruited to unattached and/or tensionless kinetochores...
  21. Ren Y, Seo H, Blobel G, Hoelz A. Structural and functional analysis of the interaction between the nucleoporin Nup98 and the mRNA export factor Rae1. Proc Natl Acad Sci U S A. 2010;107:10406-11 pubmed publisher
    ..Together, these data suggest that the Rae1*Nup98 complex directly binds to the mRNP at several stages of the mRNA export pathway. ..