Summary: The phase of cell nucleus division following PROPHASE, when the breakdown of the NUCLEAR ENVELOPE occurs and the MITOTIC SPINDLE APPARATUS enters the nuclear region and attaches to the KINETOCHORES.

Top Publications

  1. Stear J, Roth M. The Caenorhabditis elegans kinetochore reorganizes at prometaphase and in response to checkpoint stimuli. Mol Biol Cell. 2004;15:5187-96 pubmed
    ..Here, we show that the Caenorhabditis elegans kinetochore displays analogous rearrangements at prometaphase, when microtubule/chromosome interactions are being established, and after exposure to checkpoint stimuli such ..
  2. Tsuchiya D, Gonzalez C, Lacefield S. The spindle checkpoint protein Mad2 regulates APC/C activity during prometaphase and metaphase of meiosis I in Saccharomyces cerevisiae. Mol Biol Cell. 2011;22:2848-61 pubmed publisher
    ..most cells undergo both meiotic divisions, but securin, a substrate of the APC/C, is degraded prematurely, and prometaphase I/metaphase I is accelerated...
  3. Civelekoglu Scholey G, Tao L, Brust Mascher I, Wollman R, Scholey J. Prometaphase spindle maintenance by an antagonistic motor-dependent force balance made robust by a disassembling lamin-B envelope. J Cell Biol. 2010;188:49-68 pubmed publisher
    We tested the classical hypothesis that astral, prometaphase bipolar mitotic spindles are maintained by balanced outward and inward forces exerted on spindle poles by kinesin-5 and -14 using modeling of in vitro and in vivo data from ..
  4. Reis A, Madgwick S, Chang H, Nabti I, Levasseur M, Jones K. Prometaphase APCcdh1 activity prevents non-disjunction in mammalian oocytes. Nat Cell Biol. 2007;9:1192-8 pubmed
    ..APC(cdh1) was active first, during prometaphase I, and was needed in order to allow homologue congression, as loss of cdh1 speeded up MI, leading to premature ..
  5. Amador V, Ge S, Santamaria P, Guardavaccaro D, Pagano M. APC/C(Cdc20) controls the ubiquitin-mediated degradation of p21 in prometaphase. Mol Cell. 2007;27:462-73 pubmed
    ..G1/S transition, p21 proteolysis is mediated by Skp2; however, p21 reaccumulates in G2 and is degraded again in prometaphase. How p21 degradation is controlled in mitosis remains unexplored...
  6. Lane S, Yun Y, Jones K. Timing of anaphase-promoting complex activation in mouse oocytes is predicted by microtubule-kinetochore attachment but not by bivalent alignment or tension. Development. 2012;139:1947-55 pubmed publisher
    ..Our results show that stable kinetochore-microtubule attachments form in mid-prometaphase, 3-4 hours before anaphase...
  7. Huang X, Hatcher R, York J, Zhang P. Securin and separase phosphorylation act redundantly to maintain sister chromatid cohesion in mammalian cells. Mol Biol Cell. 2005;16:4725-32 pubmed
    ..Securin(-/-)separase(+/S1121A) cells are viable but fail to maintain sister chromatid cohesion in response to the disruption of spindle microtubules, show enhanced sensitivity to nocodazole, and cannot recover from prometaphase arrest.
  8. Liu J, Desai A, Onuchic J, Hwa T. An integrated mechanobiochemical feedback mechanism describes chromosome motility from prometaphase to anaphase in mitosis. Proc Natl Acad Sci U S A. 2008;105:13752-7 pubmed publisher
    ..This model can recapitulate all of the essential and distinct features of chromosome motilities from prometaphase to anaphase in a coherent manner...
  9. Peart M, Poyurovsky M, Kass E, Urist M, Verschuren E, Summers M, et al. APC/C(Cdc20) targets E2F1 for degradation in prometaphase. Cell Cycle. 2010;9:3956-64 pubmed
    ..synchronization experiments showed that siRNA directed against Cdc20 induced an accumulation of E2F1 protein in prometaphase cells...

More Information


  1. Grisan E, Poletti E, Ruggeri A. Automatic segmentation and disentangling of chromosomes in Q-band prometaphase images. IEEE Trans Inf Technol Biomed. 2009;13:575-81 pubmed publisher
    ..In order to provide the scientific community with a public dataset, the data used in this paper are available for public download. ..
  2. Gilliland W, Vietti D, Schweppe N, Guo F, Johnson T, Hawley R. Hypoxia transiently sequesters mps1 and polo to collagenase-sensitive filaments in Drosophila prometaphase oocytes. PLoS ONE. 2009;4:e7544 pubmed publisher
    ..for proper cell cycle regulation in meiosis and mitosis, localize to numerous ooplasmic filaments during prometaphase in Drosophila oocytes...
  3. Homer H, Gui L, Carroll J. A spindle assembly checkpoint protein functions in prophase I arrest and prometaphase progression. Science. 2009;326:991-4 pubmed publisher
    ..Both meiotic defects in BubR1-depleted oocytes are due to reduced activity of the master regulator known as the anaphase-promoting complex (APC), brought about through diminished levels of the APC coactivator Cdh1. ..
  4. Xiang Y, Hawley R. The mechanism of secondary nondisjunction in Drosophila melanogaster females. Genetics. 2006;174:67-78 pubmed
  5. Zachos G, Black E, Walker M, Scott M, Vagnarelli P, Earnshaw W, et al. Chk1 is required for spindle checkpoint function. Dev Cell. 2007;12:247-60 pubmed
    ..In addition, Chk1-deficient cells exhibit increased resistance to taxol. These results suggest a mechanism through which Chk1 could protect against tumorigenesis through its role in spindle checkpoint signaling. ..
  6. Orjalo A, Arnaoutov A, Shen Z, Boyarchuk Y, Zeitlin S, Fontoura B, et al. The Nup107-160 nucleoporin complex is required for correct bipolar spindle assembly. Mol Biol Cell. 2006;17:3806-18 pubmed
    ..Each antibody stained not only kinetochores but also prometaphase spindle poles and proximal spindle fibers, mirroring the dual prometaphase localization of the spindle ..
  7. Wang Y, Tsai Y, Huang J, Lee K, Kuo C, Wang C, et al. Arecoline arrests cells at prometaphase by deregulating mitotic spindle assembly and spindle assembly checkpoint: implication for carcinogenesis. Oral Oncol. 2010;46:255-62 pubmed publisher
    ..Here we reported that arecoline, a major alkaloid of areca nut, could arrest cells at prometaphase with large amounts of misaligned chromosomes...
  8. Gui L, Homer H. Hec1-dependent cyclin B2 stabilization regulates the G2-M transition and early prometaphase in mouse oocytes. Dev Cell. 2013;25:43-54 pubmed publisher
    ..These data identify another dimension to Hec1 function centered on M phase entry and early prometaphase progression and challenge the view that cyclin B2 is completely dispensable in mammals.
  9. Davydenko O, Schultz R, Lampson M. Increased CDK1 activity determines the timing of kinetochore-microtubule attachments in meiosis I. J Cell Biol. 2013;202:221-9 pubmed publisher
    ..we show that during meiosis I, attachments are regulated by CDK1 activity, which gradually increases through prometaphase and metaphase I...
  10. Kurasawa Y, Yu Lee L. PICH and cotargeted Plk1 coordinately maintain prometaphase chromosome arm architecture. Mol Biol Cell. 2010;21:1188-99 pubmed publisher
    ..we show that the Plk1-binding protein PICH and Plk1 kinase coordinately maintain chromosome architecture during prometaphase. PICH knockdown results in a loss of Plk1 from the chromosome arm and an increase in highly disorganized "wavy" ..
  11. Cai S, O Connell C, Khodjakov A, Walczak C. Chromosome congression in the absence of kinetochore fibres. Nat Cell Biol. 2009;11:832-8 pubmed publisher
    ..These bi-oriented connections are also used to maintain stable chromosome alignment at the spindle equator. ..
  12. van Zon W, Ogink J, ter Riet B, Medema R, te Riele H, Wolthuis R. The APC/C recruits cyclin B1-Cdk1-Cks in prometaphase before D box recognition to control mitotic exit. J Cell Biol. 2010;190:587-602 pubmed publisher
    The ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) is activated at prometaphase by mitotic phosphorylation and binding of its activator, Cdc20...
  13. Choi E, Lee H. Chromosome damage in mitosis induces BubR1 activation and prometaphase arrest. FEBS Lett. 2008;582:1700-6 pubmed publisher
    ..and Western blot analysis in synchronized cells, we provide evidence that DSBs activate BubR1, leading to prometaphase arrest...
  14. Magidson V, O Connell C, Loncarek J, Paul R, Mogilner A, Khodjakov A. The spatial arrangement of chromosomes during prometaphase facilitates spindle assembly. Cell. 2011;146:555-67 pubmed publisher demonstrate that unstable lateral interactions between kinetochores and microtubules dominate during early prometaphase. These transient interactions lead to the reproducible arrangement of chromosomes in an equatorial ring on the ..
  15. Wollman R, Cytrynbaum E, Jones J, Meyer T, Scholey J, Mogilner A. Efficient chromosome capture requires a bias in the 'search-and-capture' process during mitotic-spindle assembly. Curr Biol. 2005;15:828-32 pubmed
    The mitotic spindle assembles into a bipolar, microtubule-based protein machine during prometaphase. One proposed mechanism for this process is "search-and-capture," in which dynamically unstable microtubules (MTs) search space ..
  16. Gandhi R, Gillespie P, Hirano T. Human Wapl is a cohesin-binding protein that promotes sister-chromatid resolution in mitotic prophase. Curr Biol. 2006;16:2406-17 pubmed
    ..Depletion of Wapl from HeLa cells causes transient accumulation of prometaphase-like cells with chromosomes that display poorly resolved sister chromatids with a high level of cohesin...
  17. Jeganathan K, Baker D, van Deursen J. Securin associates with APCCdh1 in prometaphase but its destruction is delayed by Rae1 and Nup98 until the metaphase/anaphase transition. Cell Cycle. 2006;5:366-70 pubmed
    ..We found that Rae1 and Nup98 assemble into a complex with APC(Cdh1) in prometaphase and act to delay APC(Cdh1)-mediated ubiquitination of securin until the metaphase/anaphase transition...
  18. Choi H, Zhu B. Critical role of cyclin B1/Cdc2 up-regulation in the induction of mitotic prometaphase arrest in human breast cancer cells treated with 2-methoxyestradiol. Biochim Biophys Acta. 2012;1823:1306-15 pubmed publisher
    ..We found that 2ME(2) can selectively induce mitotic prometaphase arrest, but not G(2) phase arrest, in cultured MDA-MB-435s and MCF-7 human breast cancer cells...
  19. Menssen A, Epanchintsev A, Lodygin D, Rezaei N, Jung P, Verdoodt B, et al. c-MYC delays prometaphase by direct transactivation of MAD2 and BubR1: identification of mechanisms underlying c-MYC-induced DNA damage and chromosomal instability. Cell Cycle. 2007;6:339-52 pubmed
  20. Song S, Song M, Kim S, Kim S, Kwon S, Kim J, et al. Aurora A regulates prometaphase progression by inhibiting the ability of RASSF1A to suppress APC-Cdc20 activity. Cancer Res. 2009;69:2314-23 pubmed publisher
    ..RNA interference and expression of a nonphosphorylatable RASSF1A (S203A) mutant gene led to a marked delay in prometaphase progression...
  21. Hughes S, Gilliland W, Cotitta J, Takeo S, Collins K, Hawley R. Heterochromatic threads connect oscillating chromosomes during prometaphase I in Drosophila oocytes. PLoS Genet. 2009;5:e1000348 pubmed publisher
    ..We observed that achiasmate homologs display dynamic movements on the meiotic spindle during mid-prometaphase. An analysis of living prometaphase oocytes revealed both the rejoining of achiasmate X chromosomes initially ..
  22. Steen J, Steen H, Georgi A, Parker K, Springer M, Kirchner M, et al. Different phosphorylation states of the anaphase promoting complex in response to antimitotic drugs: a quantitative proteomic analysis. Proc Natl Acad Sci U S A. 2008;105:6069-74 pubmed publisher
    ..We examined the phosphorylation patterns of the APC in HeLa S3 cells after they were arrested in prometaphase with taxol, nocodazole, vincristine, or monastrol...
  23. Hughes S, Beeler J, Seat A, Slaughter B, Unruh J, Bauerly E, et al. Gamma-tubulin is required for bipolar spindle assembly and for proper kinetochore microtubule attachments during prometaphase I in Drosophila oocytes. PLoS Genet. 2011;7:e1002209 pubmed publisher
    ..b>Prometaphase I spindles in ?tub37C mutant oocytes showed wide, non-tapered spindle poles and disrupted positioning...
  24. Potapova T, Sivakumar S, Flynn J, Li R, Gorbsky G. Mitotic progression becomes irreversible in prometaphase and collapses when Wee1 and Cdc25 are inhibited. Mol Biol Cell. 2011;22:1191-206 pubmed publisher
    ..By inhibiting Cdk chemically, we showed that, in prometaphase, when Cdk1 substrates approach the peak of their phosphorylation, cells become capable of proper M-to-G1 ..
  25. Uetake Y, Sluder G. Prolonged prometaphase blocks daughter cell proliferation despite normal completion of mitosis. Curr Biol. 2010;20:1666-71 pubmed publisher
    ..that once the checkpoint is satisfied and cells divide, the daughter cells would proliferate regardless of prometaphase duration...
  26. Nakayama Y, Matsui Y, Takeda Y, Okamoto M, Abe K, Fukumoto Y, et al. c-Src but not Fyn promotes proper spindle orientation in early prometaphase. J Biol Chem. 2012;287:24905-15 pubmed publisher
    ..Here, we show that c-Src promotes proper spindle orientation in early prometaphase. Src localizes close to spindle poles in a manner independent of Src kinase activity...
  27. Choi H, Fukui M, Zhu B. Role of cyclin B1/Cdc2 up-regulation in the development of mitotic prometaphase arrest in human breast cancer cells treated with nocodazole. PLoS ONE. 2011;6:e24312 pubmed publisher
    ..up-regulation of cyclin B1 and Cdc2 levels, and their increases are required for the development of mitotic prometaphase arrest and characteristic phenotypes...
  28. Bolzer A, Kreth G, Solovei I, Koehler D, Saracoglu K, Fauth C, et al. Three-dimensional maps of all chromosomes in human male fibroblast nuclei and prometaphase rosettes. PLoS Biol. 2005;3:e157 pubmed
    ..We present unequivocal evidence for a probabilistic 3D order of prometaphase chromosomes, as well as of chromosome territories (CTs) in nuclei of quiescent (G0) and cycling (early S-phase) ..
  29. Schafer Hales K, Iaconelli J, Snyder J, Prussia A, Nettles J, El Naggar A, et al. Farnesyl transferase inhibitors impair chromosomal maintenance in cell lines and human tumors by compromising CENP-E and CENP-F function. Mol Cancer Ther. 2007;6:1317-28 pubmed
    ..The data show that lonafarnib in proliferating cancer cells depletes CENP-E and CENP-F from metaphase but not prometaphase kinetochores...
  30. Maia A, Lopes C, Sunkel C. BubR1 and CENP-E have antagonistic effects upon the stability of microtubule-kinetochore attachments in Drosophila S2 cell mitosis. Cell Cycle. 2007;6:1367-78 pubmed
    ..cells exit mitosis prematurely due to loss of SAC activity, CENP-meta-depleted cells accumulate in prometaphase and do not exit mitosis after spindle damage...
  31. Pulipati N, Jin Q, Liu X, Sun B, Pandey M, Huber J, et al. Overexpression of the dynein light chain km23-1 in human ovarian carcinoma cells inhibits tumor formation in vivo and causes mitotic delay at prometaphase/metaphase. Int J Cancer. 2011;129:553-64 pubmed publisher
    ..Immunofluorescence analyses demonstrated that the cells were accumulating at prometaphase/metaphase with increases in multipolar and multinucleated cells...
  32. Oceguera Yanez F, Kimura K, Yasuda S, Higashida C, Kitamura T, Hiraoka Y, et al. Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis. J Cell Biol. 2005;168:221-32 pubmed
    ..Depletion of Ect2 also impairs microtubule attachment to kinetochores and causes prometaphase delay and abnormal chromosomal segregation, as does depletion of Cdc42 or expression of the Ect2 and MgcRacGAP ..
  33. Zhang J, Hakansson H, Kuroda M, Yuan L. Wapl localization on the synaptonemal complex, a meiosis-specific proteinaceous structure that binds homologous chromosomes, in the female mouse. Reprod Domest Anim. 2008;43:124-6 pubmed publisher
    ..In the pachytene oocytes examined, mouse Wapl was colocalized with SYCP2 on the SC. Our results further implicated that Wapl might play a crucial role in meiotic chromosome remodelling at early meiosis. ..
  34. Narasimhachar Y, Webster D, Gard D, Coue M. Cdc6 is required for meiotic spindle assembly in Xenopus oocytes. Cell Cycle. 2012;11:524-31 pubmed publisher the time of germinal vesicle breakdown (GVBD), and localized to the margin of the nascent spindle early in prometaphase. Cdc6 subsequently localized to spindle poles in late prometaphase, where it remained until metaphase arrest...
  35. Carreno S, Kouranti I, Glusman E, Fuller M, Echard A, Payre F. Moesin and its activating kinase Slik are required for cortical stability and microtubule organization in mitotic cells. J Cell Biol. 2008;180:739-46 pubmed publisher
    ..Activated moesin homogenously localizes at the cortex in prometaphase and is progressively restricted at the equator in later stages...
  36. Zuccolo M, Alves A, Galy V, Bolhy S, Formstecher E, Racine V, et al. The human Nup107-160 nuclear pore subcomplex contributes to proper kinetochore functions. EMBO J. 2007;26:1853-64 pubmed
    ..Together, our data thus provide the first molecular clues underlying the function of the human Nup107-160 complex at kinetochores. ..
  37. Shamina N, Kovaleva N, Solov eva N, Gordeeva E. [Dynamics of microtubular cytoskeleton in higher plant meiosis. V. Late prometaphase. The general scheme of anastral spindle formation]. Tsitologiia. 2005;47:889-97 pubmed
    ..of cereal wide hybrids, haploids and meiotic mutants, the processes involved in cytoskeleton cycle at late prometaphase (a sub-stage of transition from chaotic figure to bipolar spindle) were studied...
  38. Listovsky T, Sale J. Sequestration of CDH1 by MAD2L2 prevents premature APC/C activation prior to anaphase onset. J Cell Biol. 2013;203:87-100 pubmed publisher
    ..In prometaphase, MAD2L2 sequestered free CDH1 away from the APC/C...
  39. McHedlishvili N, Wieser S, Holtackers R, Mouysset J, Belwal M, Amaro A, et al. Kinetochores accelerate centrosome separation to ensure faithful chromosome segregation. J Cell Sci. 2012;125:906-18 pubmed publisher
    ..However, until now, the physiological relevance of this prometaphase kinetochore pushing force was unknown...
  40. Scaife R. Microtubule disassembly and inhibition of mitosis by a novel synthetic pharmacophore. J Cell Biochem. 2006;98:102-14 pubmed
    ..Similar to other microtubule drugs, this new pharmacophore blocks mitotic spindle assembly and mitotic cell division. ..
  41. Dutrillaux A, Mercier J, Dutrillaux B. X-Y-autosome translocation, chromosome compaction, NOR expression and heterochromatin insulation in the Scarabaeid beetle Dynastes hercules hercules. Cytogenet Genome Res. 2007;116:305-10 pubmed
  42. Hirota T, Gerlich D, Koch B, Ellenberg J, Peters J. Distinct functions of condensin I and II in mitotic chromosome assembly. J Cell Sci. 2004;117:6435-45 pubmed
    ..of cohesin from chromosome arms, for chromosome shortening and for normal timing of progression through prometaphase and metaphase, whereas normal condensin II levels are dispensable for these processes...
  43. Gregory C, Maher E. Automating Giemsa banding of chromosomes: protocol for and evaluation of the use of a programmable, high-throughput automatic stainer. Biotech Histochem. 2009;84:337-45 pubmed publisher
    The use of prometaphase chromosomes prepared for high-resolution imaging is essential for accurate cytogenetic investigations...
  44. Shu T, Tseng H, Sapir T, Stern P, Zhou Y, Sanada K, et al. Doublecortin-like kinase controls neurogenesis by regulating mitotic spindles and M phase progression. Neuron. 2006;49:25-39 pubmed
    ..mechanism, DCLK regulates the formation of bipolar mitotic spindles and the proper transition from prometaphase to metaphase during mitosis...
  45. Hamta A, Adamovic T, Samuelson E, Helou K, Behboudi A, Levan G. Chromosome ideograms of the laboratory rat (Rattus norvegicus) based on high-resolution banding, and anchoring of the cytogenetic map to the DNA sequence by FISH in sample chromosomes. Cytogenet Genome Res. 2006;115:158-68 pubmed
    A detailed banded ideogram representation of the rat chromosomes was constructed based on actual G-banded prometaphase chromosomes...
  46. Vitale I, Antoccia A, Crateri P, Leone S, Arancia G, Tanzarella C. Caspase-independent apoptosis is activated by diazepam-induced mitotic failure in HeLa cells, but not in human primary fibroblasts. Apoptosis. 2005;10:909-20 pubmed
    ..In fact, differently from fibroblasts, which undergo a transient block in prophase-to-prometaphase transition, a high proportion of tumor cells attempt to escape from the DZ-imposed mitotic block, fail to ..
  47. Vaio M, Speranza P, Valls J, Guerra M, Mazzella C. Localization of the 5S and 45S rDNA sites and cpDNA sequence analysis in species of the Quadrifaria group of Paspalum (Poaceae, Paniceae). Ann Bot. 2005;96:191-200 pubmed
    ..The purpose of this research was to characterize the I genomes in five species of this group and to establish phylogenetic relationships among them...
  48. Kaczanowska J, Kaczanowski A. [Dynamics of symmetric and asymmetric mitosis and cytokinesis]. Postepy Biochem. 2010;56:29-40 pubmed
    ..elegans opens the new important research fields. ..
  49. Gao S, Giansanti M, Buttrick G, Ramasubramanyan S, Auton A, Gatti M, et al. Australin: a chromosomal passenger protein required specifically for Drosophila melanogaster male meiosis. J Cell Biol. 2008;180:521-35 pubmed publisher
  50. Pal M, Nagy O, Ménesi D, Udvardy A, Deak P. Structurally related TPR subunits contribute differently to the function of the anaphase-promoting complex in Drosophila melanogaster. J Cell Sci. 2007;120:3238-48 pubmed
    ..that these animals had an elevated level of apoptosis, high mitotic index and delayed or blocked mitosis in a prometaphase-metaphase-like state with overcondensed chromosomes...
  51. Xie C, Liu X, Yu S, Cheng C. Cardiac glycosides block cancer growth through HIF-1?- and NF-?B-mediated Plk1. Carcinogenesis. 2013;34:1870-80 pubmed publisher
    ..bufalin-treated cells exhibit a marked delay in entering prophase at an early stage and are then arrested at prometaphase or induced entry into apoptosis. This phenotypic change is attributed to the downregulation of Plk1...
  52. Hegarat L, Orsiere T, Botta A, Fessard V. Okadaic acid: chromosomal non-disjunction analysis in human lymphocytes and study of aneugenic pathway in CHO-K1 cells. Mutat Res. 2005;578:53-63 pubmed
    ..The results showed that OA induced a progressive accumulation of mitotic CHO-K1 cells in prometaphase, an induction of multipolar mitotic spindle with centrosome amplification and the formation of multinucleated ..
  53. Nabti I, Marangos P, Bormann J, Kudo N, Carroll J. Dual-mode regulation of the APC/C by CDK1 and MAPK controls meiosis I progression and fidelity. J Cell Biol. 2014;204:891-900 pubmed publisher
    ..and Cdk1 play compensatory roles to suppress the anaphase-promoting complex/cyclosome (APC/C) activity early in prometaphase, thereby allowing accumulation of APC/C substrates essential for meiosis I...