MAD1

Summary

Gene Symbol: MAD1
Description: coiled-coil domain-containing protein MAD1
Alias: coiled-coil domain-containing protein MAD1
Species: Saccharomyces cerevisiae S288c
Products:     MAD1

Top Publications

  1. Wang Y, Burke D. Checkpoint genes required to delay cell division in response to nocodazole respond to impaired kinetochore function in the yeast Saccharomyces cerevisiae. Mol Cell Biol. 1995;15:6838-44 pubmed
    ..nocodazole delay cell division under the control of the previously identified mitotic checkpoint genes BUB1, BUB3, MAD1, and MAD2 and independently of BUB2...
  2. 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. ..
  3. 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
    ..spindle defects 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...
  4. 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 ..
  5. Iouk T, Kerscher O, Scott R, Basrai M, Wozniak R. The yeast nuclear pore complex functionally interacts with components of the spindle assembly checkpoint. J Cell Biol. 2002;159:807-19 pubmed
    ..Furthermore, we show that the association of Mad1p with the NPC is not passive and that it plays a role in nuclear transport. ..
  6. Scott R, Lusk C, Dilworth D, Aitchison J, Wozniak R. Interactions between Mad1p and the nuclear transport machinery in the yeast Saccharomyces cerevisiae. Mol Biol Cell. 2005;16:4362-74 pubmed
    ..Our further analysis also showed that only the C terminus of Mad1p is required for SAC function and that the NPC, through Nup53p, may act to regulate the duration of the SAC response. ..
  7. Hardwick K, Weiss E, Luca F, Winey M, Murray A. Activation of the budding yeast spindle assembly checkpoint without mitotic spindle disruption. Science. 1996;273:953-6 pubmed
    ..Ectopic activation of cell-cycle checkpoints might be used to exploit the differences in checkpoint status between normal and tumor cells and thus improve the selectivity of chemotherapy. ..
  8. Brady D, Hardwick K. Complex formation between Mad1p, Bub1p and Bub3p is crucial for spindle checkpoint function. Curr Biol. 2000;10:675-8 pubmed
    ..Mutation of this motif abolishes checkpoint function, indicating that formation of the Mad1p-Bub1p-Bub3p complex is a crucial step in the spindle checkpoint mechanism. ..
  9. Liu H, Liang F, Jin F, Wang Y. The coordination of centromere replication, spindle formation, and kinetochore-microtubule interaction in budding yeast. PLoS Genet. 2008;4:e1000262 pubmed publisher
    ..Therefore, the shorter spindle in S-phase cells is likely to facilitate proper chromosome-microtubule interaction. ..

More Information

Publications48

  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. Farr K, Hoyt M. Bub1p kinase activates the Saccharomyces cerevisiae spindle assembly checkpoint. Mol Cell Biol. 1998;18:2738-47 pubmed
    ..MPS1, the BUB1-5 delay was dependent upon the functions of the other checkpoint genes, including BUB2 and BUB3 and MAD1, MAD2, and MAD3...
  3. Hardwick K, Murray A. Mad1p, a phosphoprotein component of the spindle assembly checkpoint in budding yeast. J Cell Biol. 1995;131:709-20 pubmed
    ..We have cloned the MAD1 gene and show that when it is disrupted yeast cells have the same phenotype as the previously isolated mad1 mutants:..
  4. Chen R, Brady D, Smith D, Murray A, Hardwick K. The spindle checkpoint of budding yeast depends on a tight complex between the Mad1 and Mad2 proteins. Mol Biol Cell. 1999;10:2607-18 pubmed
    ..Deletion and mutational analysis of both proteins indicate that association of Mad2p with Mad1p is critical for checkpoint function and for hyperphosphorylation of Mad1p...
  5. 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
    ..We discuss roles for Mad3p and its interactions with other spindle checkpoint proteins and with Cdc20p, the target of the checkpoint. ..
  6. Warren C, Brady D, Johnston R, Hanna J, Hardwick K, Spencer F. Distinct chromosome segregation roles for spindle checkpoint proteins. Mol Biol Cell. 2002;13:3029-41 pubmed
    ..Analysis of this activity indicates that the Bub3p-binding domain of Bub1p contributes to this phenotype through disruption of checkpoint activity as well as through introduction of kinetochore or spindle damage. ..
  7. Hwang W, Madhani H. Nonredundant requirement for multiple histone modifications for the early anaphase release of the mitotic exit regulator Cdc14 from nucleolar chromatin. PLoS Genet. 2009;5:e1000588 pubmed publisher
    ..The nonredundant role for these modifications in this context contrasts with the notion of a highly combinatorial code by which histone marks act to control biological processes. ..
  8. London N, Biggins S. Mad1 kinetochore recruitment by Mps1-mediated phosphorylation of Bub1 signals the spindle checkpoint. Genes Dev. 2014;28:140-52 pubmed publisher
    ..Although Mad1 kinetochore localization is the key regulatory downstream event in this cascade, its receptor and mechanism of ..
  9. Nezi L, Rancati G, De Antoni A, Pasqualato S, Piatti S, Musacchio A. Accumulation of Mad2-Cdc20 complex during spindle checkpoint activation requires binding of open and closed conformers of Mad2 in Saccharomyces cerevisiae. J Cell Biol. 2006;174:39-51 pubmed
    ..C-Mad2 forms when Mad2 binds its checkpoint target Cdc20 or its kinetochore receptor Mad1. When unbound to these ligands, Mad2 folds as O-Mad2...
  10. Muñoz Barrera M, Aguilar I, Monje Casas F. Dispensability of the SAC Depends on the Time Window Required by Aurora B to Ensure Chromosome Biorientation. PLoS ONE. 2015;10:e0144972 pubmed publisher
  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. Murillo Pineda M, Cabello Lobato M, Clemente Ruiz M, Monje Casas F, Prado F. Defective histone supply causes condensin-dependent chromatin alterations, SAC activation and chromosome decatenation impairment. Nucleic Acids Res. 2014;42:12469-82 pubmed publisher
    ..Therefore, our results reveal the importance of a precise interplay between histone supply and condensin/Top2 for pericentric chromatin structure, precatenanes resolution and centromere biorientation. ..
  13. Campbell C, Desai A. Tension sensing by Aurora B kinase is independent of survivin-based centromere localization. Nature. 2013;497:118-21 pubmed publisher
    ..These results suggest that activation of Aurora B kinase by clustering either on chromatin or on microtubules is sufficient for chromosome biorientation...
  14. Mayer M, Pot I, Chang M, Xu H, Aneliunas V, Kwok T, et al. Identification of protein complexes required for efficient sister chromatid cohesion. Mol Biol Cell. 2004;15:1736-45 pubmed
    ..Furthermore, we find that genes involved in mitotic spindle integrity and positioning have a previously unrecognized role in sister chromatid cohesion. ..
  15. Ólafsson G, Thorpe P. Synthetic Physical Interactions Map Kinetochore-Checkpoint Activation Regions. G3 (Bethesda). 2016;6:2531-42 pubmed publisher
    ..The recruitment of the Mad1 and Mad2 proteins to the kinetochore is normally necessary for SAC activation...
  16. Li Z, Vizeacoumar F, Bahr S, Li J, Warringer J, Vizeacoumar F, et al. Systematic exploration of essential yeast gene function with temperature-sensitive mutants. Nat Biotechnol. 2011;29:361-7 pubmed publisher
    ..This mutant collection should facilitate a wide range of systematic studies aimed at understanding the functions of essential genes. ..
  17. Rossio V, Galati E, Ferrari M, Pellicioli A, Sutani T, Shirahige K, et al. The RSC chromatin-remodeling complex influences mitotic exit and adaptation to the spindle assembly checkpoint by controlling the Cdc14 phosphatase. J Cell Biol. 2010;191:981-97 pubmed publisher
    ..Our data suggest that fine-tuning regulators of mitotic exit have important functions during mitotic progression in cells treated with microtubule poisons and might be promising targets for cancer treatment. ..
  18. 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. ..
  19. Scott R, Cairo L, Van de Vosse D, Wozniak R. The nuclear export factor Xpo1p targets Mad1p to kinetochores in yeast. J Cell Biol. 2009;184:21-9 pubmed publisher
    ..These results reveal an important function for Xpo1p in mediating intranuclear transport events and identify a signaling pathway between kinetochores and NPCs. ..
  20. Hosotani T, Koyama H, Uchino M, Miyakawa T, Tsuchiya E. PKC1, a protein kinase C homologue of Saccharomyces cerevisiae, participates in microtubule function through the yeast EB1 homologue, BIM1. Genes Cells. 2001;6:775-88 pubmed
    ..These results suggest that Pkc1p plays a role which is relevant to microtubule functions and that this role is mediated by a hitherto unknown PKC signalling pathway and by Bim1p ..
  21. 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.
  22. D Amours D, Stegmeier F, Amon A. Cdc14 and condensin control the dissolution of cohesin-independent chromosome linkages at repeated DNA. Cell. 2004;117:455-69 pubmed
    ..This dual role of the FEAR network in initiating mitotic exit and promoting chromosome segregation ensures that exit from mitosis is coupled to the completion of chromosome segregation. ..
  23. Jiang Y. An essential role of Tap42-associated PP2A and 2A-like phosphatases in Ty1 transcriptional silencing of S. cerevisiae. Yeast. 2008;25:755-64 pubmed publisher
    ..PP2A holoenzyme activity, which is independent of Tap42 and TORC1, is not essential for Ty1 transcriptional silencing, strengthening the argument that TORC1-specific signalling underlies Ty1 transcriptional silencing. ..
  24. Barnhart E, Dorer R, Murray A, Schuyler S. Reduced Mad2 expression keeps relaxed kinetochores from arresting budding yeast in mitosis. Mol Biol Cell. 2011;22:2448-57 pubmed publisher
    ..The Mad1-Mad2 complex is an essential component of the checkpoint...
  25. Horigome C, Okada T, Shimazu K, Gasser S, Mizuta K. Ribosome biogenesis factors bind a nuclear envelope SUN domain protein to cluster yeast telomeres. EMBO J. 2011;30:3799-811 pubmed publisher
    ..Our results suggest that the ribosome biogenesis factors Ebp2 and Rrs1 cooperate with Mps3 to mediate telomere clustering, but not telomere tethering, by binding Sir4. ..
  26. Cairo L, Ptak C, Wozniak R. Mitosis-specific regulation of nuclear transport by the spindle assembly checkpoint protein Mad1p. Mol Cell. 2013;49:109-20 pubmed publisher
    ..We propose that a distinct branch of the SAC exists in which Mad1p senses unattached kinetochores and, by altering NPC transport activity, regulates the nuclear environment of the spindle. ..
  27. Robinson L, Phillips J, Brou L, Boswell E, Tatchell K. Suppressors of ipl1-2 in components of a Glc7 phosphatase complex, Cdc48 AAA ATPase, TORC1, and the kinetochore. G3 (Bethesda). 2012;2:1687-701 pubmed publisher
    ..The slow growth and cell cycle delay of ndc80-K204E cells are partially alleviated by the ipl1-2 mutation. These data provide biological confirmation of a biochemically based model for the effect of phosphorylation on Ndc80 function. ..
  28. Thu Y, Van Riper S, Higgins L, Zhang T, Becker J, Markowski T, et al. Slx5/Slx8 Promotes Replication Stress Tolerance by Facilitating Mitotic Progression. Cell Rep. 2016;15:1254-65 pubmed publisher
    ..Based on these findings, we propose a model in which Slx5/8 allows for passage through mitosis when replication stress is tolerable. ..
  29. Clift D, Bizzari F, Marston A. Shugoshin prevents cohesin cleavage by PP2A(Cdc55)-dependent inhibition of separase. Genes Dev. 2009;23:766-80 pubmed publisher
    ..We propose that Cdc55 is a separase inhibitor that acts downstream from Shugoshin under conditions where sister chromatids are not under tension. ..
  30. Angus Hill M, Schlichter A, Roberts D, Erdjument Bromage H, Tempst P, Cairns B. A Rsc3/Rsc30 zinc cluster dimer reveals novel roles for the chromatin remodeler RSC in gene expression and cell cycle control. Mol Cell. 2001;7:741-51 pubmed
    ..We propose that Rsc3 and Rsc30 interact physically but have different roles in targeting or regulating RSC. ..
  31. Krefman N, Drubin D, Barnes G. Control of the spindle checkpoint by lateral kinetochore attachment and limited Mad1 recruitment. Mol Biol Cell. 2015;26:2620-39 pubmed publisher
    We observed the dynamic recruitment of spindle checkpoint proteins Mad1 and Bub1 to detached kinetochores in budding yeast using real-time live-cell imaging and quantified recruitment in fixed cells...
  32. 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
    The spindle checkpoint governs the timing of anaphase separation of sister chromatids. In budding yeast, Mad1, Mad2, and Mad3 proteins are equally required for arrest in the presence of damage induced by antimicrotubule drugs or ..
  33. Laflamme G, Tremblay Boudreault T, Roy M, Andersen P, Bonneil E, Atchia K, et al. Structural maintenance of chromosome (SMC) proteins link microtubule stability to genome integrity. J Biol Chem. 2014;289:27418-31 pubmed publisher
    ..Collectively, these findings demonstrate that SMC proteins can bind to and stabilize microtubules and that SMC-microtubule interactions are essential to establish a robust system to maintain genome integrity. ..
  34. Kastenmayer J, Lee M, Hong A, Spencer F, Basrai M. The C-terminal half of Saccharomyces cerevisiae Mad1p mediates spindle checkpoint function, chromosome transmission fidelity and CEN association. Genetics. 2005;170:509-17 pubmed
    ..Using partial mad1 deletion alleles we determined that the C-terminal half of Mad1p is necessary and sufficient for checkpoint ..
  35. Anderson V, Prudden J, Prochnik S, Giddings T, Hardwick K. Novel sfi1 alleles uncover additional functions for Sfi1p in bipolar spindle assembly and function. Mol Biol Cell. 2007;18:2047-56 pubmed
    ..With the aim of identifying novel mitotic defects we carried out a mad1 synthetic lethal screen in budding yeast. In this screen, four novel alleles of sfi1 were isolated...
  36. Aravamudhan P, Chen R, Roy B, Sim J, Joglekar A. Dual mechanisms regulate the recruitment of spindle assembly checkpoint proteins to the budding yeast kinetochore. Mol Biol Cell. 2016;27:3405-3417 pubmed
    ..Spc105 then recruits the Bub3-Bub1 and Mad1-Mad2 complexes, which produce the inhibitory signal that arrests cell division...
  37. Jin F, Liu H, Li P, Yu H, Wang Y. Loss of function of the Cik1/Kar3 motor complex results in chromosomes with syntelic attachment that are sensed by the tension checkpoint. PLoS Genet. 2012;8:e1002492 pubmed publisher
    ..Therefore, we can induce syntelic attachments in budding yeast by inactivating the Cik1/Kar3 complex, and this approach will be very useful to study the checkpoint response to syntelic attachments...
  38. Matsuda K, Makise M, Sueyasu Y, Takehara M, Asano T, Mizushima T. Yeast two-hybrid analysis of the origin recognition complex of Saccharomyces cerevisiae: interaction between subunits and identification of binding proteins. FEMS Yeast Res. 2007;7:1263-9 pubmed
    ..We discuss roles of these interactions in functions of ORC. ..
  39. 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. ..