Genomes and Genes
Gene Symbol: mad2
Description: spindle checkpoint protein Mad2
Alias: spindle checkpoint protein Mad2
Species: fission yeast
- Ohi M, Feoktistova A, Ren L, Yip C, Cheng Y, Chen J, et al. Structural organization of the anaphase-promoting complex bound to the mitotic activator Slp1. Mol Cell. 2007;28:871-85 pubmed..Comparison of the APC/C with another multiprotein E3 ligase, the SCF complex, uncovers remarkable structural similarities. ..
- Sczaniecka M, Feoktistova A, May K, Chen J, Blyth J, Gould K, et al. The spindle checkpoint functions of Mad3 and Mad2 depend on a Mad3 KEN box-mediated interaction with Cdc20-anaphase-promoting complex (APC/C). J Biol Chem. 2008;283:23039-47 pubmed publisher..In the fission yeast, Schizosaccharomyces pombe, we find that the Mad3 and Mad2 spindle checkpoint proteins interact stably with the APC/C in mitosis...
- Heinrich S, Geissen E, Kamenz J, Trautmann S, Widmer C, Drewe P, et al. Determinants of robustness in spindle assembly checkpoint signalling. Nat Cell Biol. 2013;15:1328-39 pubmed publisher..Our work highlights low gene expression noise as an important determinant of reliable checkpoint signalling. ..
- Vardy L, Toda T. The fission yeast gamma-tubulin complex is required in G(1) phase and is a component of the spindle assembly checkpoint. EMBO J. 2000;19:6098-111 pubmed..Furthermore, alp4mad2 double mutants show an exaggerated multiple septation phenotype in TBZ. These results indicate that Alp4 and Alp6 may play a crucial role in the spindle pole-mediated checkpoint pathway. ..
- Heinrich S, Windecker H, Hustedt N, Hauf S. Mph1 kinetochore localization is crucial and upstream in the hierarchy of spindle assembly checkpoint protein recruitment to kinetochores. J Cell Sci. 2012;125:4720-7 pubmed publisher..a three-layered hierarchy with Ark1 and Mph1 on top, Bub1 and Bub3 in the middle, and Mad3 as well as the Mad1-Mad2 complex at the lower end of the hierarchy...
- Garcia M, Koonrugsa N, Toda T. Spindle-kinetochore attachment requires the combined action of Kin I-like Klp5/6 and Alp14/Dis1-MAPs in fission yeast. EMBO J. 2002;21:6015-24 pubmed..In klp5 mutants, spindle checkpoint proteins Mad2 and Bub1 are recruited to mitotic kinetochores for a prolonged duration, indicating that these kinetochores are ..
- Saitoh S, Kobayashi Y, Ogiyama Y, Takahashi K. Dual regulation of Mad2 localization on kinetochores by Bub1 and Dam1/DASH that ensure proper spindle interaction. Mol Biol Cell. 2008;19:3885-97 pubmed publisher..Although checkpoint proteins, such as Mad2, are localized on kinetochores that do not interact properly with the spindle, it remains unknown how the ..
- Toyoda Y, Furuya K, Goshima G, Nagao K, Takahashi K, Yanagida M. Requirement of chromatid cohesion proteins rad21/scc1 and mis4/scc2 for normal spindle-kinetochore interaction in fission yeast. Curr Biol. 2002;12:347-58 pubmed..The loss of chromatid cohesion in fission yeast mutants (mis4-242 and rad21-K1) leads to the activation of Mad2- and Bub1-dependent checkpoint, possibly due to a diminished microtubule-kinetochore interaction...
- Sato M, Koonrugsa N, Toda T, Vardy L, Tournier S, Millar J. Deletion of Mia1/Alp7 activates Mad2-dependent spindle assembly checkpoint in fission yeast. Nat Cell Biol. 2003;5:764-6; author reply 766 pubmed
- He X, Jones M, Winey M, Sazer S. Mph1, a member of the Mps1-like family of dual specificity protein kinases, is required for the spindle checkpoint in S. pombe. J Cell Sci. 1998;111 ( Pt 12):1635-47 pubmed..mph1 functions upstream of mad2, a previously characterized component of the spindle checkpoint...
- Kim S, Lin D, Matsumoto S, Kitazono A, Matsumoto T. Fission yeast Slp1: an effector of the Mad2-dependent spindle checkpoint. Science. 1998;279:1045-7 pubmedb>Mad2 is a component of the spindle checkpoint, which delays the onset of anaphase until all chromosomes are attached to the spindle...
- Kadura S, He X, Vanoosthuyse V, Hardwick K, Sazer S. 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. Mol Biol Cell. 2005;16:385-95 pubmed..These data indicate that Bub1p-A78V is defective in both nuclear accumulation and kinetochore targeting and that a threshold level of nuclear Bub1p is necessary for the nuclear accumulation of Bub3p and Mad3p. ..
- Zheng L, Schwartz C, Wee L, Oliferenko S. The fission yeast transforming acidic coiled coil-related protein Mia1p/Alp7p is required for formation and maintenance of persistent microtubule-organizing centers at the nuclear envelope. Mol Biol Cell. 2006;17:2212-22 pubmed..When microtubule polymerization was allowed, MTOCs were efficiently assembled de novo. We propose a model where MTOC emergence is a self-organizing process requiring the continuous association of microtubules with nucleation sites. ..
- Syrovatkina V, Fu C, Tran P. Antagonistic spindle motors and MAPs regulate metaphase spindle length and chromosome segregation. Curr Biol. 2013;23:2423-9 pubmed publisher..Removing these proteins in antagonistic combination rescued the defective spindle length and in some combinations also partially rescued chromosome segregation defects. ..
- Millband D, Hardwick K. 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. Mol Cell Biol. 2002;22:2728-42 pubmed..We discuss the implications of these findings in the context of our current understanding of spindle checkpoint function. ..
- Ikui A, Furuya K, Yanagida M, Matsumoto T. Control of localization of a spindle checkpoint protein, Mad2, in fission yeast. J Cell Sci. 2002;115:1603-10 pubmed..b>Mad2, a component of the checkpoint, targets fission yeast Slp1/budding yeast Cdc20/human p55CDC and prevents it from ..
- Kimata Y, Matsuyama A, Nagao K, Furuya K, Obuse C, Yoshida M, et al. Diminishing HDACs by drugs or mutations promotes normal or abnormal sister chromatid separation by affecting APC/C and adherin. J Cell Sci. 2008;121:1107-18 pubmed publisher..HATs and HDACs might directly target adherin and APC/C to ensure proper chromosome segregation, and anti-tumour effects of HDAC inhibitors could be attributed to this deregulation. ..
- Pidoux A, Richardson W, Allshire R. Sim4: a novel fission yeast kinetochore protein required for centromeric silencing and chromosome segregation. J Cell Biol. 2003;161:295-307 pubmed..Our analyses illustrate the fundamental link between silencing, chromatin structure, and kinetochore function, and establish defective silencing as a powerful approach for identifying proteins required to build a functional kinetochore. ..
- Fedyanina O, Mardanov P, Tokareva E, McIntosh J, Grishchuk E. Chromosome segregation in fission yeast with mutations in the tubulin folding cofactor D. Curr Genet. 2006;50:281-94 pubmed..This and other genetic interactions between cofactor D mutants and specific kinetochore and spindle components suggest their critical role in establishing the normal kinetochore-microtubule interface. ..
- Shimada M, Yamamoto A, Murakami Tonami Y, Nakanishi M, Yoshida T, Aiba H, et al. Casein kinase II is required for the spindle assembly checkpoint by regulating Mad2p in fission yeast. Biochem Biophys Res Commun. 2009;388:529-32 pubmed publisher..are sensitive to the microtubule depolymerising drug thiabendazole, which is counteracted by ectopic expression of mad2+. The level of Mad2p is low in the CK2 mutants...
- Win T, Mankouri H, Hickson I, Wang S. A role for the fission yeast Rqh1 helicase in chromosome segregation. J Cell Sci. 2005;118:5777-84 pubmed..This mitotic delay is dependent on the spindle checkpoint, as deletion of mad2 abolishes the delay as well as the accumulation of Cut2 in rqh1delta cells...
- Herring M, Davenport N, Stephan K, Campbell S, White R, Kark J, et al. Fission yeast Rad26ATRIP delays spindle-pole-body separation following interphase microtubule damage. J Cell Sci. 2010;123:1537-45 pubmed publisher..This response to microtubule damage delays spindle-pole-body separation and, in doing so, might preserve both cellular morphology and chromosome stability. ..
- Tang N, Toda T. Alp7/TACC recruits kinesin-8-PP1 to the Ndc80 kinetochore protein for timely mitotic progression and chromosome movement. J Cell Sci. 2015;128:354-63 pubmed publisher..We propose that the recruitment of kinesin-8-PP1 to the kinetochore through Alp7/TACC interaction plays a crucial role in regulation of timely mitotic progression and chromosome movement during anaphase A. ..
- Zich J, Sochaj A, Syred H, Milne L, Cook A, Ohkura H, et al. Kinase activity of fission yeast Mph1 is required for Mad2 and Mad3 to stably bind the anaphase promoting complex. Curr Biol. 2012;22:296-301 pubmed publisher..b>Mad2 is a key checkpoint component that undergoes conformational activation, catalyzed by a Mad1-Mad2 template enriched ..
- Sonkar A, Yadav S, Ahmed S. Cleavage and polyadenylation factor, Rna14 is an essential protein required for the maintenance of genomic integrity in fission yeast Schizosaccharomyces pombe. Biochim Biophys Acta. 2016;1863:189-97 pubmed publisher..These findings reveal the importance of transcription termination in the maintenance of genomic stability through the regulation of kinetochore function. ..
- Kerres A, Jakopec V, Beuter C, Karig I, Pöhlmann J, Pidoux A, et al. Fta2, an essential fission yeast kinetochore component, interacts closely with the conserved Mal2 protein. Mol Biol Cell. 2006;17:4167-78 pubmed..However, Fta2 kinetochore localization is reduced in a spc7 mutant. Spc7, a suppressor of the EB1 family member Mal3, is part of the conserved Ndc80-MIND-Spc7 kinetochore complex. ..
- Nakano A, Masuda K, Hiromoto T, Takahashi K, Matsumoto Y, Habib A, et al. Rad51-dependent aberrant chromosome structures at telomeres and ribosomal DNA activate the spindle assembly checkpoint. Mol Cell Biol. 2014;34:1389-97 pubmed publisher..In both cases, Mad2 foci persisted longer than usual at kinetochores, suggesting a defect in kinetochore-microtubule attachment...
- Tanaka K, Yonekawa T, Kawasaki Y, Kai M, Furuya K, Iwasaki M, et al. Fission yeast Eso1p is required for establishing sister chromatid cohesion during S phase. Mol Cell Biol. 2000;20:3459-69 pubmed..The C-terminal region acts to establish sister chromatid cohesion, and the N-terminal region presumably catalyzes translesion DNA synthesis when template DNA contains lesions that block regular DNA replication. ..
- Sugimoto I, Murakami H, Tonami Y, Moriyama A, Nakanishi M. DNA replication checkpoint control mediated by the spindle checkpoint protein Mad2p in fission yeast. J Biol Chem. 2004;279:47372-8 pubmed..In the presence of the DNA replication inhibitor hydroxyurea (HU), cds1 mad2 cells entered and progressed through mitosis earlier than did cds1 cells...
- Hirai H, Arai K, Kariyazono R, Yamamoto M, Sato M. The kinetochore protein Kis1/Eic1/Mis19 ensures the integrity of mitotic spindles through maintenance of kinetochore factors Mis6/CENP-I and CENP-A. PLoS ONE. 2014;9:e111905 pubmed publisher..Thus, we propose an unexpected relationship between inner kinetochore organization and spindle integrity. ..
- Singh G, Karade S, Ranjan R, Ahamad N, Ahmed S. C-terminal region of Mad2 plays an important role during mitotic spindle checkpoint in fission yeast Schizosaccharomyces pombe. Mol Biol Rep. 2017;44:89-96 pubmed publisherThe mitotic arrest deficiency 2 (Mad2) protein is an essential component of the spindle assembly checkpoint that interacts with Cdc20/Slp1 and inhibit its ability to activate anaphase promoting complex/cyclosome (APC/C)...
- Murakami H, Goto D, Toda T, Chen E, Grewal S, Martienssen R, et al. Ribonuclease activity of Dis3 is required for mitotic progression and provides a possible link between heterochromatin and kinetochore function. PLoS ONE. 2007;2:e317 pubmed..This block is dependent on the Mad2 checkpoint protein...
- Mayer C, Filopei J, Batac J, Alford L, Paluh J. An extended anaphase signaling pathway for Mad2p includes microtubule organizing center proteins and multiple motor-dependent transitions. Cell Cycle. 2006;5:1456-63 pubmed..Our findings indicate that altered Mad2p anaphase spindle localizations can reflect changes in spindle function during mitotic exit that could contribute to fidelity in anaphase events...
- Alao J, Huis In t Veld P, Buhse F, Sunnerhagen P. Hyperosmosis enhances radiation and hydroxyurea resistance of Schizosaccharomyces pombe checkpoint mutants through the spindle checkpoint and delayed cytokinesis. Mol Microbiol. 2010;77:143-57 pubmed publisher..A delay in G2/M is dependent on Srk1. Progression through mitosis is halted by the Mad2-dependent spindle checkpoint. Finally, cytokinesis is impaired by modulating Cdc25 expression...
- Zhou L, Watts F. Nep1, a Schizosaccharomyces pombe deneddylating enzyme. Biochem J. 2005;389:307-14 pubmed..Our results suggest that, in vivo, Nep1 may be responsible for deneddylating proteins other than cullins. ..
- Funaya C, Samarasinghe S, Pruggnaller S, Ohta M, Connolly Y, Muller J, et al. Transient structure associated with the spindle pole body directs meiotic microtubule reorganization in S. pombe. Curr Biol. 2012;22:562-74 pubmed publisher..This ensures rMT dissolution and bipolar spindle formation. Our study reveals the molecular basis for the transient generation of a novel MTOC, which triggers a program of MT rearrangement that is required for meiotic differentiation. ..
- Kerres A, Jakopec V, Fleig U. The conserved Spc7 protein is required for spindle integrity and links kinetochore complexes in fission yeast. Mol Biol Cell. 2007;18:2441-54 pubmed..spc7 mutant phenotypes were partially rescued by extra alpha-tubulin or extra Mal2. Thus, Spc7 interacts genetically with the Mal2-containing Sim4 complex. ..
- Minoda A, Saitoh S, Takahashi K, Toda T. BAF53/Arp4 homolog Alp5 in fission yeast is required for histone H4 acetylation, kinetochore-spindle attachment, and gene silencing at centromere. Mol Biol Cell. 2005;16:316-27 pubmed..Mitotic arrest is ascribable to activation of the Mad2/Bub1 spindle checkpoint, in which both proteins localize to the mitotic kinetochores in alp5-1134...
- Garcia M, Koonrugsa N, Toda T. Two kinesin-like Kin I family proteins in fission yeast regulate the establishment of metaphase and the onset of anaphase A. Curr Biol. 2002;12:610-21 pubmed..Furthermore, the mitotic extension is dependent upon the Mad2 spindle checkpoint. We discuss two models of Kin I function in fission yeast...
- Xu X, Nakazawa N, Yanagida M. Condensin HEAT subunits required for DNA repair, kinetochore/centromere function and ploidy maintenance in fission yeast. PLoS ONE. 2015;10:e0119347 pubmed publisher..Five of these mutations reside in helix B of HEAT repeats. Two non-SMC condensin subunits, Cnd1 and Cnd3, are thus implicated in ploidy maintenance. ..
- Yang H, Asakawa H, Haraguchi T, Hiraoka Y. Nup132 modulates meiotic spindle attachment in fission yeast by regulating kinetochore assembly. J Cell Biol. 2015;211:295-308 pubmed publisher..Thus, we propose that Nup132 plays an important role in establishing monopolar spindle attachment at meiosis I through outer kinetochore reorganization at meiotic prophase. ..
- Zich J, May K, Paraskevopoulos K, Sen O, Syred H, van der Sar S, et al. Mps1Mph1 Kinase Phosphorylates Mad3 to Inhibit Cdc20Slp1-APC/C and Maintain Spindle Checkpoint Arrests. PLoS Genet. 2016;12:e1005834 pubmed publisher..This genetic dissection of APC/C inhibition demonstrates that Mps1(Mph1) kinase-dependent modifications of Mad3 and Mad2 act in a concerted manner to maintain spindle checkpoint arrests.
- Bernard P, Drogat J, Dheur S, Genier S, Javerzat J. Splicing factor Spf30 assists exosome-mediated gene silencing in fission yeast. Mol Cell Biol. 2010;30:1145-57 pubmed publisher..We propose that Spf30, bound to nascent centromeric transcripts, perhaps with other splicing factors, assists their processing by the exosome. Splicing factor intercession may thus be a common feature of gene silencing pathways. ..
- Topolski B, Jakopec V, Künzel N, Fleig U. Inositol Pyrophosphate Kinase Asp1 Modulates Chromosome Segregation Fidelity and Spindle Function in Schizosaccharomyces pombe. Mol Cell Biol. 2016;36:3128-3140 pubmed..In fact, the chromosome transmission fidelity of a nonessential chromosome was enhanced with increased cellular IPPs. Thus, we identified an element that optimized the wild-type chromosome transmission process. ..
- Sakuno T, Tanaka K, Hauf S, Watanabe Y. Repositioning of aurora B promoted by chiasmata ensures sister chromatid mono-orientation in meiosis I. Dev Cell. 2011;21:534-45 pubmed publisher..Our results elucidate how chiasmata favor biorientation of bivalents over that of univalents at meiosis I...
- Tange Y, Kurabayashi A, Goto B, Hoe K, Kim D, Park H, et al. The CCR4-NOT complex is implicated in the viability of aneuploid yeasts. PLoS Genet. 2012;8:e1002776 pubmed publisher..In addition, our findings suggest that the genes required for homologous recombination repair are important for aneuploid viability. ..
- Mulvihill D, Hyams J. Cytokinetic actomyosin ring formation and septation in fission yeast are dependent on the full recruitment of the polo-like kinase Plo1 to the spindle pole body and a functional spindle assembly checkpoint. J Cell Sci. 2002;115:3575-86 pubmed..in response to loss of microtubule integrity was abolished in cells lacking the spindle assembly checkpoint protein Mad2 or containing non-functional Cdc16, a component of the fission yeast septation initiation network (SIN)...
- Heinrich S, Sewart K, Windecker H, Langegger M, Schmidt N, Hustedt N, et al. Mad1 contribution to spindle assembly checkpoint signalling goes beyond presenting Mad2 at kinetochores. EMBO Rep. 2014;15:291-8 pubmed publisher..A complex between the checkpoint proteins Mad1 and Mad2 provides a platform for Mad2:Mad2 dimerization at unattached kinetochores, which enables Mad2 to delay anaphase...
- Horikoshi Y, Habu T, Matsumoto T. An E2 enzyme Ubc11 is required for ubiquitination of Slp1/Cdc20 and spindle checkpoint silencing in fission yeast. Cell Cycle. 2013;12:961-71 pubmed publisher..We propose that each of the two E2 enzymes is responsible for collaborating with APC/C for a specific set of substrates, and that Ubc11 is responsible for regulating Slp1 with APC/C for silencing the SAC. ..
- Ito D, Saito Y, Matsumoto T. Centromere-tethered Mps1 pombe homolog (Mph1) kinase is a sufficient marker for recruitment of the spindle checkpoint protein Bub1, but not Mad1. Proc Natl Acad Sci U S A. 2012;109:209-14 pubmed publisher..Although the components of the checkpoint such as Bub1, Mad1 and Mad2 selectively accumulate at unattached kinetochores, the answer to how they recognize unattached kinetochores has ..
- Hirose Y, Suzuki R, Ohba T, Hinohara Y, Matsuhara H, Yoshida M, et al. Chiasmata promote monopolar attachment of sister chromatids and their co-segregation toward the proper pole during meiosis I. PLoS Genet. 2011;7:e1001329 pubmed publisher..Based on these results, we propose that chiasmata play a pivotal role in the selection of proper attachments and provide a backup mechanism that promotes correct chromosome segregation when improper attachments remain during anaphase I...
- Goldstone S, Reyes C, Gay G, Courtheoux T, Dubarry M, Tournier S, et al. Tip1/CLIP-170 protein is required for correct chromosome poleward movement in fission yeast. PLoS ONE. 2010;5:e10634 pubmed publisher..Our results suggest that S. pombe Tip1/CLIP170 is directly or indirectly required for correct chromosome poleward movement independently of Mal3/EB1. ..
- Petersen J, Hagan I. S. pombe aurora kinase/survivin is required for chromosome condensation and the spindle checkpoint attachment response. Curr Biol. 2003;13:590-7 pubmed..However, it was required for two aspects of Mad2 function that accompany checkpoint activation: full-scale association with kinetochores and formation of a complex ..
- Sewart K, Hauf S. Different Functionality of Cdc20 Binding Sites within the Mitotic Checkpoint Complex. Curr Biol. 2017;27:1213-1220 pubmed publisher..the human MCC binds two Cdc20 molecules, one (Cdc20M) through well-characterized, cooperative binding to Mad2 and Mad3/BubR1 (forming the "core MCC") and the other one (Cdc20A) through additional binding sequences ..
- Hou H, Zhou Z, Wang Y, Wang J, Kallgren S, Kurchuk T, et al. Csi1 links centromeres to the nuclear envelope for centromere clustering. J Cell Biol. 2012;199:735-44 pubmed publisher..These studies thus define a molecular link between the centromere and nuclear envelope that is responsible for centromere clustering...
- Choi S, Péli Gulli M, Mcleod I, Sarkeshik A, Yates J, Simanis V, et al. Phosphorylation state defines discrete roles for monopolin in chromosome attachment and spindle elongation. Curr Biol. 2009;19:985-95 pubmed publisher..Together, these findings illustrate how the sequential phosphorylation and dephosphorylation of monopolin helps ensure the orderly execution of discrete steps in mitosis. ..