Gene Symbol: mad2
Description: mad2
Alias: CG17498, Dmel\CG17498, MAD2, Mad2, mad2, CG17498-PA, mad2-PA
Species: fruit fly
Products:     mad2

Top Publications

  1. Li D, Morley G, Whitaker M, Huang J. Recruitment of Cdc20 to the kinetochore requires BubR1 but not Mad2 in Drosophila melanogaster. Mol Cell Biol. 2010;30:3384-95 pubmed publisher
    ..This checkpoint involves the kinetochore proteins Mad2, BubR1, and Cdc20. Mad2 and BubR1 are inhibitors of the APC/C, but Cdc20 is an activator...
  2. Pandey R, Heeger S, Lehner C. Rapid effects of acute anoxia on spindle kinetochore interactions activate the mitotic spindle checkpoint. J Cell Sci. 2007;120:2807-18 pubmed
    ..Although involving adenosine triphosphate (ATP)-consuming kinases, the spindle checkpoint can therefore be activated by spindle damage in response to acute anoxia and protect against aneuploidies. ..
  3. Buffin E, Emre D, Karess R. Flies without a spindle checkpoint. Nat Cell Biol. 2007;9:565-72 pubmed
    b>Mad2 has a key role in the spindle-assembly checkpoint (SAC) - the mechanism delaying anaphase onset until all chromosomes correctly attach to the spindle...
  4. Buffin E, Lefebvre C, Huang J, Gagou M, Karess R. Recruitment of Mad2 to the kinetochore requires the Rod/Zw10 complex. Curr Biol. 2005;15:856-61 pubmed
    ..The dynamics of Rod and Mad2, examined in different organisms, show intriguing similarities as well as apparent differences...
  5. Emre D, Terracol R, Poncet A, Rahmani Z, Karess R. A mitotic role for Mad1 beyond the spindle checkpoint. J Cell Sci. 2011;124:1664-71 pubmed publisher
    ..Mad1 is the receptor for Mad2 at kinetochores, where it catalyzes the formation of Mad2-Cdc20 complexes, an essential part of the anaphase ..
  6. Katsani K, Karess R, Dostatni N, Doye V. In vivo dynamics of Drosophila nuclear envelope components. Mol Biol Cell. 2008;19:3652-66 pubmed publisher
    ..Finally, we examined the dynamics of the spindle checkpoint proteins Mad2 and Mad1...
  7. Logarinho E, Bousbaa H, Dias J, Lopes C, Amorim I, Antunes Martins A, et al. Different spindle checkpoint proteins monitor microtubule attachment and tension at kinetochores in Drosophila cells. J Cell Sci. 2004;117:1757-71 pubmed
    ..Here, we analyse how the kinetochore localization of the Drosophila spindle checkpoint proteins Bub1, Mad2, Bub3 and BubR1, behave in response to alterations in microtubule binding or tension...
  8. Orr B, Bousbaa H, Sunkel C. Mad2-independent spindle assembly checkpoint activation and controlled metaphase-anaphase transition in Drosophila S2 cells. Mol Biol Cell. 2007;18:850-63 pubmed
    ..We analyzed the role of the putative Drosophila Mad2 homologue in the spindle assembly checkpoint and mitotic progression...
  9. Mendiburo M, Padeken J, Fülöp S, Schepers A, Heun P. Drosophila CENH3 is sufficient for centromere formation. Science. 2011;334:686-90 pubmed publisher
    ..We conclude that CID is both necessary and sufficient to serve as an epigenetic centromere mark and nucleate heritable centromere function...

More Information


  1. Lince Faria M, Maffini S, Orr B, Ding Y, Cláudia Florindo -, Sunkel C, et al. Spatiotemporal control of mitosis by the conserved spindle matrix protein Megator. J Cell Biol. 2009;184:647-57 pubmed publisher
    ..nuclear pore complex protein translocated promoter region (Tpr), and the spindle assembly checkpoint (SAC) protein Mad2 form a conserved complex that localizes to a nuclear derived spindle matrix in living cells...
  2. Przewloka M, Venkei Z, Bolanos Garcia V, Debski J, Dadlez M, Glover D. CENP-C is a structural platform for kinetochore assembly. Curr Biol. 2011;21:399-405 pubmed publisher
    ..Thus, the N-terminal part of Drosophila CENP-C is sufficient to recruit core kinetochore components and acts as the principal linkage between centromere and kinetochore during mitosis. ..
  3. Rahmani Z, Gagou M, Lefebvre C, Emre D, Karess R. Separating the spindle, checkpoint, and timer functions of BubR1. J Cell Biol. 2009;187:597-605 pubmed publisher
    ..In contrast, bubR1-KEN flies have normal spindles but no SAC. Nevertheless, mitotic timing is normal as long as Mad2 is present. Thus, the SAC, timer, and spindle functions of BubR1 are substantially separable...
  4. Karess R. Rod-Zw10-Zwilch: a key player in the spindle checkpoint. Trends Cell Biol. 2005;15:386-92 pubmed
    ..for the recruitment of two better-known components of the kinetochore--the dynein-dynactin complex, and Mad1-Mad2. It has now been established that RZZ is directly or indirectly responsible for both Mad1-Mad2 recruitment to ..
  5. Basto R, Brunk K, Vinadogrova T, Peel N, Franz A, Khodjakov A, et al. Centrosome amplification can initiate tumorigenesis in flies. Cell. 2008;133:1032-42 pubmed publisher
    ..Thus, centrosome amplification can initiate tumorigenesis in flies. ..
  6. Liu D, Shaukat Z, Saint R, Gregory S. Chromosomal instability triggers cell death via local signalling through the innate immune receptor Toll. Oncotarget. 2015;6:38552-65 pubmed publisher
    ..This pathway also activates Mmp1, which recruits hemocytes to the CIN tissue to provide local amplification of the immune response that is needed for effective elimination of CIN cells. ..
  7. Royou A, Gagou M, Karess R, Sullivan W. BubR1- and Polo-coated DNA tethers facilitate poleward segregation of acentric chromatids. Cell. 2010;140:235-45 pubmed publisher
    ..We propose that BubR1 and Polo facilitate the accurate segregation of acentric chromatids by maintaining the integrity of the tethers that connect acentric chromosomes to their centric partners. ..
  8. Schweizer N, Pawar N, Weiss M, Maiato H. An organelle-exclusion envelope assists mitosis and underlies distinct molecular crowding in the spindle region. J Cell Biol. 2015;210:695-704 pubmed publisher
    ..differences in molecular crowding states that are sufficient to drive accumulation of mitotic regulators, such as Mad2 and Megator/Tpr, as well as soluble tubulin, in the spindle region...
  9. Conde C, Osswald M, Barbosa J, Moutinho Santos T, Pinheiro D, Guimaraes S, et al. Drosophila Polo regulates the spindle assembly checkpoint through Mps1-dependent BubR1 phosphorylation. EMBO J. 2013;32:1761-77 pubmed publisher
    ..We propose a model in which Polo controls Mps1-dependent BubR1 phosphorylation to promote Cdc20 kinetochore recruitment and sustained SAC function. ..
  10. Griffis E, Stuurman N, Vale R. Spindly, a novel protein essential for silencing the spindle assembly checkpoint, recruits dynein to the kinetochore. J Cell Biol. 2007;177:1005-15 pubmed
    ..In higher eukaryotes, cytoplasmic dynein is involved in silencing the SAC by removing the checkpoint proteins Mad2 and the Rod-Zw10-Zwilch complex (RZZ) from aligned kinetochores (Howell, B.J., B.F. McEwen, J.C. Canman, D.B...
  11. Caous R, Pascal A, Romé P, Richard Parpaillon L, Karess R, Giet R. Spindle assembly checkpoint inactivation fails to suppress neuroblast tumour formation in aurA mutant Drosophila. Nat Commun. 2015;6:8879 pubmed publisher
    ..The monitoring of Mad2 and cyclin B dynamics in live aurA NBs reveals that SAC satisfaction is not coupled to cyclin B degradation...
  12. Venkei Z, Yamashita Y. The centrosome orientation checkpoint is germline stem cell specific and operates prior to the spindle assembly checkpoint in Drosophila testis. Development. 2015;142:62-9 pubmed publisher
    ..This study may provide a framework for identifying and understanding similar mechanisms that might be in place in other asymmetrically dividing cell types. ..
  13. Feijão T, Afonso O, Maia A, Sunkel C. Stability of kinetochore-microtubule attachment and the role of different KMN network components in Drosophila. Cytoskeleton (Hoboken). 2013;70:661-75 pubmed publisher
  14. Batiha O, Swan A. Evidence that the spindle assembly checkpoint does not regulate APC(Fzy) activity in Drosophila female meiosis. Genome. 2012;55:63-7 pubmed publisher
    ..We found that loss of function mutations in SAC genes, Mad2, zwilch, and mps1, do not lead to the predicted rise in APC(Fzy)-dependent degradation of cyclin B either globally ..
  15. Stormo B, Fox D. Distinct responses to reduplicated chromosomes require distinct Mad2 responses. elife. 2016;5: pubmed publisher
    ..Both reduplication responses require the spindle assembly checkpoint protein Mad2. While Mad2 delays anaphase separation of metaphase polytene chromosomes, Mad2's control of overall mitotic timing ..
  16. Gogendeau D, Siudeja K, Gambarotto D, Pennetier C, Bardin A, Basto R. Aneuploidy causes premature differentiation of neural and intestinal stem cells. Nat Commun. 2015;6:8894 pubmed publisher
    ..Our work highlights a neural and intestine stem cell-specific response to aneuploidy, which prevents their proliferation and expansion. ..
  17. Williamson A, Wickliffe K, Mellone B, Song L, Karpen G, Rape M. Identification of a physiological E2 module for the human anaphase-promoting complex. Proc Natl Acad Sci U S A. 2009;106:18213-8 pubmed publisher
    ..We conclude that UbcH10 and Ube2S constitute a physiological E2-module for APC/C, the activity of which is required for spindle assembly and cell division. ..
  18. McCleland M, Shermoen A, O Farrell P. DNA replication times the cell cycle and contributes to the mid-blastula transition in Drosophila embryos. J Cell Biol. 2009;187:7-14 pubmed publisher
    ..We conclude that normal S phase and replication checkpoint activities are important timers of the undisturbed cell cycle before, but not after, the MBT...
  19. Herriott A, Sweeney M, Whitaker M, Taggart M, Huang J. Kinetochore localized Mad2 and Cdc20 is itself insufficient for triggering the mitotic checkpoint when Mps1 is low in Drosophila melanogaster neuroblasts. Cell Cycle. 2012;11:4650-60 pubmed publisher
    ..Here, we report the characterization of the in vivo behavior of Cdc20 and Mad2 and the relevant spindle assembly checkpoint (SAC) functions in the neuroblasts of a Drosophila Mps1 weak allele (..
  20. Liu Y, Singh S, Zeng X, Zhao J, Hou S. The Nuclear Matrix Protein Megator Regulates Stem Cell Asymmetric Division through the Mitotic Checkpoint Complex in Drosophila Testes. PLoS Genet. 2015;11:e1005750 pubmed publisher
    ..Expression of mitotic arrest-deficient-2 (Mad2) and monopolar spindle 1 (Mps1) of the SAC complex effectively rescued the GSC loss phenotype associated with loss ..
  21. Althoff F, Karess R, Lehner C. Spindle checkpoint-independent inhibition of mitotic chromosome segregation by Drosophila Mps1. Mol Biol Cell. 2012;23:2275-91 pubmed publisher
    ..This delay in metaphase depends on the SAC component Mad2. Although Mps1 overexpression in mad2 mutants no longer causes a metaphase delay, it perturbs anaphase...
  22. Chen C, Dechassa M, Bettini E, Ledoux M, Belisario C, Heun P, et al. CAL1 is the Drosophila CENP-A assembly factor. J Cell Biol. 2014;204:313-29 pubmed publisher
    ..Collectively, this work identifies the "missing" CENP-A chaperone in flies, revealing fundamental conservation between insect and vertebrate centromere-specification mechanisms. ..
  23. Morais da Silva S, Moutinho Santos T, Sunkel C. A tumor suppressor role of the Bub3 spindle checkpoint protein after apoptosis inhibition. J Cell Biol. 2013;201:385-93 pubmed publisher
    ..Our data suggest that Bub3 has a nonkinetochore-dependent function that is consistent with its role as a tumor suppressor. ..
  24. Delgehyr N, Wieland U, Rangone H, Pinson X, Mao G, Dzhindzhev N, et al. Drosophila Mgr, a Prefoldin subunit cooperating with von Hippel Lindau to regulate tubulin stability. Proc Natl Acad Sci U S A. 2012;109:5729-34 pubmed publisher
    ..Thus, Vhl may play a pivotal role: promoting microtubule stabilization when tubulins are correctly folded by Prefoldin and tubulin destruction when they are not. ..
  25. Oliveira R, Hamilton R, Pauli A, Davis I, Nasmyth K. Cohesin cleavage and Cdk inhibition trigger formation of daughter nuclei. Nat Cell Biol. 2010;12:185-92 pubmed publisher
    ..We conclude that only two key events, opening of cohesin rings and downregulation of Cdk1, are sufficient to drive proper segregation of chromosomes in anaphase. ..
  26. Andrejka L, Wen H, Ashton J, Grant M, Iori K, Wang A, et al. Animal-specific C-terminal domain links myeloblastosis oncoprotein (Myb) to an ancient repressor complex. Proc Natl Acad Sci U S A. 2011;108:17438-43 pubmed publisher
    ..Therefore, our results imply that the specific interaction of the C terminus of Myb with the MuvB/dREAM core complex may provide an attractive target for the development of cancer therapeutics. ..
  27. Kwon M, Godinho S, Chandhok N, Ganem N, Azioune A, Thery M, et al. Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes. Genes Dev. 2008;22:2189-203 pubmed publisher
    ..Thus, morphological features of cancer cells can be linked to unique genetic requirements for survival. ..
  28. Schittenhelm R, Chaleckis R, Lehner C. Intrakinetochore localization and essential functional domains of Drosophila Spc105. EMBO J. 2009;28:2374-86 pubmed publisher
    ..Spc105 seems to provide a platform within the outer kinetochore allowing independent assembly of various kinetochore components. ..
  29. Défachelles L, Raich N, Terracol R, Baudin X, Williams B, Goldberg M, et al. RZZ and Mad1 dynamics in Drosophila mitosis. Chromosome Res. 2015;23:333-42 pubmed publisher
    ..In addition, we report that a fraction of RZZ and Mad1 can co-immunoprecipitate, indicating that the genetically determined recruitment hierarchy (in which Mad1 depends on RZZ) may reflect a physical association of the two complexes. ..
  30. Rubin T, Karess R, Rahmani Z. Cenp-meta is required for sustained spindle checkpoint. Biol Open. 2014;3:522-8 pubmed publisher
    ..cenp-meta? mutant cells display a mitotic delay. Yet, despite the persistence of the two checkpoint proteins Mad2 and BubR1 on unattached kinetochores, these cells eventually enter anaphase and give rise to highly aneuploid ..
  31. Ding Y, Yao C, Lince Faria M, Rath U, Cai W, Maiato H, et al. Chromator is required for proper microtubule spindle formation and mitosis in Drosophila. Dev Biol. 2009;334:253-63 pubmed publisher
  32. Matos I, Pereira A, Lince Faria M, Cameron L, Salmon E, Maiato H. Synchronizing chromosome segregation by flux-dependent force equalization at kinetochores. J Cell Biol. 2009;186:11-26 pubmed publisher
    ..We propose that flux-dependent equalization of kinetochore tensions ensures a timely and uniform maturation of kinetochore-microtubule interfaces necessary for error-free and coordinated segregation of chromosomes in anaphase. ..
  33. Mische S, He Y, Ma L, Li M, Serr M, Hays T. Dynein light intermediate chain: an essential subunit that contributes to spindle checkpoint inactivation. Mol Biol Cell. 2008;19:4918-29 pubmed publisher
    ..S2 cells does not block the recruitment of a dynein complex to kinetochores, but it does delay inactivation of Mad2 signaling and mitotic progression...
  34. Ghosh A, Shimell M, Leof E, Haley M, O Connor M. UPRT, a suicide-gene therapy candidate in higher eukaryotes, is required for Drosophila larval growth and normal adult lifespan. Sci Rep. 2015;5:13176 pubmed publisher
    ..Our findings also suggest that expression of the endogenous UPRT gene will likely cause background incorporation when using microbial UPRT as a cell-specific mRNA labeling reagent in higher eukaryotes. ..
  35. Ebrahimi S, Fraval H, Murray M, Saint R, Gregory S. Polo kinase interacts with RacGAP50C and is required to localize the cytokinesis initiation complex. J Biol Chem. 2010;285:28667-73 pubmed publisher
    ..Our results indicate that Polo kinase directly binds the conserved cytokinesis initiation complex and is required to trigger centralspindlin localization as a first step in cytokinesis. ..
  36. Orr B, Sunkel C. Drosophila CENP-C is essential for centromere identity. Chromosoma. 2011;120:83-96 pubmed publisher
    ..We suggest that CENP-C might fulfill the structural roles of the human centromere-associated proteins not identified in Drosophila. ..
  37. Williams B, Leung G, Maiato H, Wong A, Li Z, Williams E, et al. Mitch a rapidly evolving component of the Ndc80 kinetochore complex required for correct chromosome segregation in Drosophila. J Cell Sci. 2007;120:3522-33 pubmed
    ..Despite the crucial role of Mitch in cell division, the mitch gene has evolved very rapidly among species in the genus Drosophila. ..
  38. Défachelles L, Hainline S, Menant A, Lee L, Karess R. A maternal effect rough deal mutation suggests that multiple pathways regulate Drosophila RZZ kinetochore recruitment. J Cell Sci. 2015;128:1204-16 pubmed publisher
    Proper kinetochore recruitment and regulation of dynein and the Mad1-Mad2 complex requires the Rod-Zw10-Zwilch (RZZ) complex...
  39. Rodrigues N, Lekomtsev S, Jananji S, Kriston Vizi J, Hickson G, Baum B. Kinetochore-localized PP1-Sds22 couples chromosome segregation to polar relaxation. Nature. 2015;524:489-92 pubmed publisher
  40. Mirkovic M, Hutter L, Novák B, Oliveira R. Premature Sister Chromatid Separation Is Poorly Detected by the Spindle Assembly Checkpoint as a Result of System-Level Feedback. Cell Rep. 2015;13:469-478 pubmed publisher
    ..Our findings explain how cohesion defects may escape SAC surveillance. ..
  41. Wong H, Shaukat Z, Wang J, Saint R, Gregory S. JNK signaling is needed to tolerate chromosomal instability. Cell Cycle. 2014;13:622-31 pubmed publisher
    ..Our findings suggest that chromosomal instability represents a significant stress to dividing cells, and that without JNK signaling, cells undergo apoptosis because they lack a timely and effective response to DNA damage. ..
  42. Hickson G, O Farrell P. Rho-dependent control of anillin behavior during cytokinesis. J Cell Biol. 2008;180:285-94 pubmed publisher
    ..We propose that such interactions occur dynamically and transiently to promote furrow stability. ..
  43. Gallaud E, Caous R, Pascal A, Bazile F, Gagné J, Huet S, et al. Ensconsin/Map7 promotes microtubule growth and centrosome separation in Drosophila neural stem cells. J Cell Biol. 2014;204:1111-21 pubmed publisher
    ..In addition, Ensconsin promotes microtubule polymerization during mitosis to control spindle length independent of Kinesin-1. ..
  44. Milan M, Clemente Ruiz M, Dekanty A, Muzzopappa M. Aneuploidy and tumorigenesis in Drosophila. Semin Cell Dev Biol. 2014;28:110-5 pubmed publisher
    ..Here we discuss the role of aneuploidy in tumorigenesis in light of the contribution of Drosophila epithelial cancer models and propose a stress-induced tumor-promoting role of aneuploidy. ..
  45. Meisel R, Hilldorfer B, Koch J, Lockton S, Schaeffer S. Adaptive evolution of genes duplicated from the Drosophila pseudoobscura neo-X chromosome. Mol Biol Evol. 2010;27:1963-78 pubmed publisher
  46. Müller H, Fogeron M, Lehmann V, Lehrach H, Lange B. A centrosome-independent role for gamma-TuRC proteins in the spindle assembly checkpoint. Science. 2006;314:654-7 pubmed
    ..However, their localization at the centrosome and centrosome integrity were not essential for this function. Thus, the spindle checkpoint can be activated at the level of microtubule nucleation. ..
  47. Cane S, McGilvray P, Maresca T. Insights from an erroneous kinetochore-microtubule attachment state. Bioarchitecture. 2013;3:69-76 pubmed publisher
    ..Our force-related studies are also discussed in the context of current models for tension-dependent stabilization of kt-MT interactions. ..
  48. Poulton J, Cuningham J, Peifer M. Acentrosomal Drosophila epithelial cells exhibit abnormal cell division, leading to cell death and compensatory proliferation. Dev Cell. 2014;30:731-45 pubmed publisher
    ..These data reveal the importance of centrosomes in fly epithelia and demonstrate the robust compensatory mechanisms at the cellular and organismal level. ..