Genomes and Genes
Gene Symbol: MAD2
Description: spindle checkpoint protein MAD2
Alias: spindle checkpoint protein MAD2
Species: Saccharomyces cerevisiae S288c
- Cheng Y, Chen R. The AAA-ATPase Cdc48 and cofactor Shp1 promote chromosome bi-orientation by balancing Aurora B activity. J Cell Sci. 2010;123:2025-34 pubmed publisher..Our results identify Cdc48 and Shp1 as critical components that balance the kinase and phosphatase activities at the kinetochore in order to achieve stable bipolar attachment. ..
- Keck J, Jones M, Wong C, Binkley J, Chen D, Jaspersen S, et al. A cell cycle phosphoproteome of the yeast centrosome. Science. 2011;332:1557-61 pubmed publisher..Our work establishes the extent and complexity of this prominent posttranslational modification in centrosome biology and provides specific examples of phosphorylation control in centrosome function. ..
- Cheeseman I, Enquist Newman M, MULLER REICHERT T, Drubin D, Barnes G. Mitotic spindle integrity and kinetochore function linked by the Duo1p/Dam1p complex. J Cell Biol. 2001;152:197-212 pubmed..In addition, Duo1p and Dam1p localize to kinetochores in chromosome spreads, suggesting that this complex may serve as a link between the kinetochore and the mitotic spindle. ..
- 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. ..
- 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. ..
- Hyland K, Kingsbury J, Koshland D, Hieter P. Ctf19p: A novel kinetochore protein in Saccharomyces cerevisiae and a potential link between the kinetochore and mitotic spindle. J Cell Biol. 1999;145:15-28 pubmed..We propose that Ctf19p is part of a macromolecular kinetochore complex, which may function as a link between the kinetochore and the mitotic spindle. ..
- 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..The checkpoint protein Mad2 (mitotic arrest deficient 2) adopts two conformations: open (O-Mad2) and closed (C-Mad2)...
- Indjeian V, Stern B, Murray A. The centromeric protein Sgo1 is required to sense lack of tension on mitotic chromosomes. Science. 2005;307:130-3 pubmed
- Krishnan V, Nirantar S, Crasta K, Cheng A, Surana U. DNA replication checkpoint prevents precocious chromosome segregation by regulating spindle behavior. Mol Cell. 2004;16:687-700 pubmed..ability to prevent nuclear division is abolished by combined deficiency of microtubule-destabilizing motor Kip3 and Mad2 functions...
- Pinsky B, Tatsutani S, Collins K, Biggins S. An Mtw1 complex promotes kinetochore biorientation that is monitored by the Ipl1/Aurora protein kinase. Dev Cell. 2003;5:735-45 pubmed..We therefore propose that an Mtw1 complex is required for kinetochore biorientation that is monitored by the Ipl1p kinase. ..
- Camasses A, Bogdanova A, Shevchenko A, Zachariae W. The CCT chaperonin promotes activation of the anaphase-promoting complex through the generation of functional Cdc20. Mol Cell. 2003;12:87-100 pubmed..We propose that folding of the Cdc20 family of APC/C activators is an essential and evolutionary conserved function of the CCT chaperonin. ..
- Lin T, Gombos L, Neuner A, Sebastian D, Olsen J, Hrle A, et al. Phosphorylation of the yeast ?-tubulin Tub4 regulates microtubule function. PLoS ONE. 2011;6:e19700 pubmed publisher..Three phosphorylation sites in Tub4 were found to be critical for Tub4 stability and microtubule organization. One of the sites is highly conserved in ?-tubulins from yeast to human. ..
- Ross K, COHEN FIX O. The role of Cdh1p in maintaining genomic stability in budding yeast. Genetics. 2003;165:489-503 pubmed..CDH1 showed genetic interactions with MAD2 and PDS1, genes encoding components of the mitotic spindle assembly checkpoint that acts at metaphase to prevent ..
- 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..sister chromatid separation solely by inhibiting APCCdc20-dependent Pds1 proteolysis and that this process requires Mad2. Blocking APCCdh1-mediated Clb2 proteolysis and chromosome re-duplication does not require Mad2 but a different ..
- Farr K, Hoyt M. Bub1p kinase activates the Saccharomyces cerevisiae spindle assembly checkpoint. Mol Cell Biol. 1998;18:2738-47 pubmed..the BUB1-5 delay was dependent upon the functions of the other checkpoint genes, including BUB2 and BUB3 and MAD1, MAD2, and MAD3...
- Kitazono A, Garza D, Kron S. Mutations in the yeast cyclin-dependent kinase Cdc28 reveal a role in the spindle assembly checkpoint. Mol Genet Genomics. 2003;269:672-84 pubmed..Genetic interactions with checkpoint and apc mutants suggest Cdc28 may regulate checkpoint arrest downstream of the MAD2 and BUB2 pathways...
- Pan J, Chen R. Spindle checkpoint regulates Cdc20p stability in Saccharomyces cerevisiae. Genes Dev. 2004;18:1439-51 pubmed..Our study suggests that the spindle checkpoint reduces Cdc20p to below a certain threshold level to ensure a complete inhibition of Cdc20p before anaphase. ..
- Rosenberg J, Cross F, Funabiki H. KNL1/Spc105 recruits PP1 to silence the spindle assembly checkpoint. Curr Biol. 2011;21:942-7 pubmed publisher..We propose that the PP1-Spc105 interaction enables local regulation of dynamic phosphorylation and dephosphorylation at the kinetochore to couple microtubule attachment and SAC silencing...
- 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. ..
- 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 pubmedThe 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 ..
- Fraschini R, Formenti E, Lucchini G, Piatti S. Budding yeast Bub2 is localized at spindle pole bodies and activates the mitotic checkpoint via a different pathway from Mad2. J Cell Biol. 1999;145:979-91 pubmed..localizes at the spindle pole body (SPB) throughout the cell cycle; (b) the effect of concomitant lack of Mad1 or Mad2 and Bub2 is additive, since nocodazole-treated mad1 bub2 and mad2 bub2 double mutants rereplicate DNA more rapidly ..
- Kemmler S, Stach M, Knapp M, Ortiz J, Pfannstiel J, Ruppert T, et al. Mimicking Ndc80 phosphorylation triggers spindle assembly checkpoint signalling. EMBO J. 2009;28:1099-110 pubmed publisher..Therefore, we conclude that a putative Mps1-dependent phosphorylation of Ndc80 is important for SAC activation at kinetochores. ..
- 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...
- 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. ..
- 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..delay cell division under the control of the previously identified mitotic checkpoint genes BUB1, BUB3, MAD1, and MAD2 and independently of BUB2...
- 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
- Severin F, Hyman A, Piatti S. Correct spindle elongation at the metaphase/anaphase transition is an APC-dependent event in budding yeast. J Cell Biol. 2001;155:711-8 pubmed..Our data suggest that stabilization of the elongating spindle at the metaphase to anaphase transition involves Pds1-dependent targets other than Esp1. ..
- 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. ..
- Maringele L, Lydall D. EXO1-dependent single-stranded DNA at telomeres activates subsets of DNA damage and spindle checkpoint pathways in budding yeast yku70Delta mutants. Genes Dev. 2002;16:1919-33 pubmed..We have also found that the MAD2 but not the BUB2 spindle checkpoint gene is required for efficient arrest of yku70Delta mutants...
- 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...
- Page A, Aneliunas V, Lamb J, Hieter P. In vivo characterization of the nonessential budding yeast anaphase-promoting complex/cyclosome components Swm1p, Mnd2p and Apc9p. Genetics. 2005;170:1045-62 pubmed..Furthermore, the role of Apc9p in APC/C-dependent ubiquitination may be limited to the proteolysis of a select number of substrates. ..
- 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, ..
- Lyons N, Morgan D. Cdk1-dependent destruction of Eco1 prevents cohesion establishment after S phase. Mol Cell. 2011;42:378-89 pubmed publisher..We also show that deregulation of Eco1 results in chromosome separation defects in anaphase. We conclude that this regulatory mechanism helps optimize the level of sister chromatid cohesion, ensuring a robust and efficient anaphase. ..
- Chai C, Teh E, Yeong F. Unrestrained spindle elongation during recovery from spindle checkpoint activation in cdc15-2 cells results in mis-segregation of chromosomes. Mol Biol Cell. 2010;21:2384-98 pubmed publisher..Our data indicate that a slower rate of transition through the cell division cycle can result in an inadequate level of Pds1p accumulation that can compromise recovery from spindle assembly checkpoint activation. ..
- Shonn M, McCarroll R, Murray A. Spo13 protects meiotic cohesin at centromeres in meiosis I. Genes Dev. 2002;16:1659-71 pubmed..Overexpressing the mitotic cohesin, Scc1/Mcd1, does not substitute for Rec8, suggesting that the combined actions of Spo13 and Rec8 are important for preventing sister centromere separation in meiosis I. ..
- 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. ..
- Ohkuni K, Abdulle R, Tong A, Boone C, Kitagawa K. Ybp2 associates with the central kinetochore of Saccharomyces cerevisiae and mediates proper mitotic progression. PLoS ONE. 2008;3:e1617 pubmed publisher..Ybp2 seems to be part of a macromolecular kinetochore complex and appears to contribute to the proper associations among the central kinetochore subcomplexes and the kinetochore-specific nucleosome. ..
- Akiyoshi B, Nelson C, Biggins S. The aurora B kinase promotes inner and outer kinetochore interactions in budding yeast. Genetics. 2013;194:785-9 pubmed publisher..The Dsn1 component is crucial for kinetochore assembly and is phosphorylated by the Aurora B kinase. We found that Aurora B phosphorylation of Dsn1 promotes the interaction between outer and inner kinetochore proteins in budding yeast. ..
- 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...
- Leisner C, Kammerer D, Denoth A, Britschi M, Barral Y, Liakopoulos D. Regulation of mitotic spindle asymmetry by SUMO and the spindle-assembly checkpoint in yeast. Curr Biol. 2008;18:1249-55 pubmed publisher..checkpoint (SAC) due to SUMO and kinetochore defects promoted symmetric redistribution of Kar9 in a Mad2-dependent manner...
- Hwang H, Song K. IBD2 encodes a novel component of the Bub2p-dependent spindle checkpoint in the budding yeast Saccharomyces cerevisiae. Genetics. 2002;161:595-609 pubmed..The mitotic arrest defects of ibd2Delta were not recovered by MAD2, or vice versa...
- Makhnevych T, Wong P, Pogoutse O, Vizeacoumar F, Greenblatt J, Emili A, et al. Hsp110 is required for spindle length control. J Cell Biol. 2012;198:623-36 pubmed publisher..These data suggest a model whereby the Hsp70-Hsp110 chaperone complex antagonizes Cin8 plus-end motility and prevents premature spindle elongation in S phase. ..
- Hotz M, Leisner C, Chen D, Manatschal C, Wegleiter T, Ouellet J, et al. Spindle pole bodies exploit the mitotic exit network in metaphase to drive their age-dependent segregation. Cell. 2012;148:958-72 pubmed publisher..We propose that MEN signaling links Kar9 regulation to SPB identity through biasing and stabilizing the age-insensitive, cyclin-B-dependent mechanism of symmetry breaking. ..
- Simonetta M, Manzoni R, Mosca R, Mapelli M, Massimiliano L, Vink M, et al. The influence of catalysis on mad2 activation dynamics. PLoS Biol. 2009;7:e10 pubmed publisherb>Mad2 is a key component of the spindle assembly checkpoint, a safety device ensuring faithful sister chromatid separation in mitosis. The target of Mad2 is Cdc20, an activator of the anaphase-promoting complex/cyclosome (APC/C)...
- Gibson D, Bell S, Aparicio O. Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae. Genes Cells. 2006;11:557-73 pubmed..We discuss the potential significance of these overlapping checkpoints and the impact of our findings on previously postulated role(s) of ORCs in other cell cycle functions. ..
- Caudron F, Denarier E, Thibout Quintana J, Brocard J, Andrieux A, Fourest Lieuvin A. Mutation of Ser172 in yeast ? tubulin induces defects in microtubule dynamics and cell division. PLoS ONE. 2010;5:e13553 pubmed publisher..In the absence of Mad2p-dependent spindle checkpoint, both mutations are deleterious. These findings show the importance of Ser172 for the correct function of both cytoplasmic and spindle MTs and for normal cell division. ..
- Gómez González B, Felipe Abrio I, Aguilera A. The S-phase checkpoint is required to respond to R-loops accumulated in THO mutants. Mol Cell Biol. 2009;29:5203-13 pubmed publisher..In light of these results, we propose a model in which R-loop-mediated recombination is explained by template switching. ..
- Xu H, Boone C, Brown G. Genetic dissection of parallel sister-chromatid cohesion pathways. Genetics. 2007;176:1417-29 pubmed
- Cairo L, Wozniak R. The Nuclear Transport Factor Kap121 Is Required for Stability of the Dam1 Complex and Mitotic Kinetochore Bi-orientation. Cell Rep. 2016;14:2440-50 pubmed publisher..We propose that Kap121 stabilizes the Dam1 complex and participates in escorting it to spindle MTs. ..
- Karumbati A, Wilson T. Abrogation of the Chk1-Pds1 checkpoint leads to tolerance of persistent single-strand breaks in Saccharomyces cerevisiae. Genetics. 2005;169:1833-44 pubmed..We propose a model in which recombinational repair during S phase coupled with failure of the metaphase-anaphase checkpoint allows for tolerance of persistent single-strand breaks at the expense of genome stability. ..
- Cuschieri L, Miller R, Vogel J. Gamma-tubulin is required for proper recruitment and assembly of Kar9-Bim1 complexes in budding yeast. Mol Biol Cell. 2006;17:4420-34 pubmed..We propose that SPBs, via the tail of Tub4, promote the assembly of functional +TIP complexes before their deployment to microtubule +ends. ..
- Peng Y, Wong C, Nakajima Y, Tyers R, Sarkeshik A, Yates J, et al. Overlapping kinetochore targets of CK2 and Aurora B kinases in mitotic regulation. Mol Biol Cell. 2011;22:2680-9 pubmed publisher..Furthermore, we show Mif2 and the inner kinetochore protein Ndc10 are phosphorylated by CK2, and this phosphorylation plays antagonistic and synergistic roles with Aurora B phosphorylation of these targets, respectively. ..
- Ikui A, Cross F. Specific genetic interactions between spindle assembly checkpoint proteins and B-Type cyclins in Saccharomyces cerevisiae. Genetics. 2009;183:51-61 pubmed publisher..However, another spindle checkpoint gene, MAD2, could be deleted without ill effects in the absence of CLB5, suggesting that the bub1/3 clb5 synthetic lethality ..
- Lee M, Bakir A, Nguyen K, Bachant J. The SUMO isopeptidase Ulp2p is required to prevent recombination-induced chromosome segregation lethality following DNA replication stress. PLoS Genet. 2011;7:e1001355 pubmed publisher..At the same time, Ulp2p is also required to either suppress or resolve recombination-induced attachments between sister chromatids. These opposing defects may synergize to greatly increase the toxicity of DNA replication stress. ..
- Suzuki M, Igarashi R, Sekiya M, Utsugi T, Morishita S, Yukawa M, et al. Dynactin is involved in a checkpoint to monitor cell wall synthesis in Saccharomyces cerevisiae. Nat Cell Biol. 2004;6:861-71 pubmed..Components of the dynactin complex are required to achieve the G2 arrest whilst keeping cells highly viable. Thus, the dynactin complex has a function in a checkpoint that monitors cell wall synthesis. ..
- Lin T, Neuner A, Schlosser Y, Scharf A, Weber L, Schiebel E. Cell-cycle dependent phosphorylation of yeast pericentrin regulates ?-TuSC-mediated microtubule nucleation. elife. 2014;3:e02208 pubmed publisher..The two types of ?-TuCRs contain distinct but conserved C-terminal MTOC targeting domains.DOI: http://dx.doi.org/10.7554/eLife.02208.001. ..
- 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. ..
- Jin F, Wang Y. The signaling network that silences the spindle assembly checkpoint upon the establishment of chromosome bipolar attachment. Proc Natl Acad Sci U S A. 2013;110:21036-41 pubmed publisher..Therefore, Sgo1, Ipl1 kinase, Dam1, and protein phosphatase 1 comprise the SAC silencing network that ensures the correct timing for anaphase onset...
- Bizzari F, Marston A. Cdc55 coordinates spindle assembly and chromosome disjunction during meiosis. J Cell Biol. 2011;193:1213-28 pubmed publisher..Therefore, Cdc55 orders passage through the meiotic divisions by ensuring a balance of phosphatases. ..
- Strawn L, True H. Deletion of RNQ1 gene reveals novel functional relationship between divergently transcribed Bik1p/CLIP-170 and Sfi1p in spindle pole body separation. Curr Genet. 2006;50:347-66 pubmed..These results suggest that Bik1p has a previously uncharacterized function in the separation of duplicated SPBs. ..
- Jiang Y, Ferro Novick S. Identification of yeast component A: reconstitution of the geranylgeranyltransferase that modifies Ypt1p and Sec4p. Proc Natl Acad Sci U S A. 1994;91:4377-81 pubmed..Thus, these findings suggest that there is one essential escort protein in yeast, while more than one may exist in mammalian cells...
- Fesquet D, Fitzpatrick P, Johnson A, Kramer K, Toyn J, Johnston L. A Bub2p-dependent spindle checkpoint pathway regulates the Dbf2p kinase in budding yeast. EMBO J. 1999;18:2424-34 pubmed..Our data now point to the protein kinase Mps1p triggering a new parallel branch of the spindle checkpoint in which Bub2p blocks Dbf2p function. ..
- Dotiwala F, Harrison J, Jain S, Sugawara N, Haber J. Mad2 prolongs DNA damage checkpoint arrest caused by a double-strand break via a centromere-dependent mechanism. Curr Biol. 2010;20:328-32 pubmed publisher..Here we report that Mad2 and other SAC proteins play an unexpected role in prolonging G2/M arrest after induction of a single DSB...
- Lai L, Morabito L, Holloway S. A novel yeast mutant that is defective in regulation of the Anaphase-Promoting Complex by the spindle damage checkpoint. Mol Genet Genomics. 2003;270:156-64 pubmed..This is the first demonstration that a mutation in a core APC/C subunit can result in a MAD2-dependent arrest at the restrictive temperature...
- Hotz M, Lengefeld J, Barral Y. The MEN mediates the effects of the spindle assembly checkpoint on Kar9-dependent spindle pole body inheritance in budding yeast. Cell Cycle. 2012;11:3109-16 pubmed publisher..Together, our study indicates that Clb5 functions in spindle assembly and that the SAC controls the specification and inheritance of yeast SPBs through inhibition of the MEN. ..
- 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..The Mad1 interaction with Bub1 and kinetochores can be reconstituted in the presence of Mps1 and Mad2. Together, this work reveals a critical mechanism that determines kinetochore activation of the spindle checkpoint. ..