RCC1-Ran-RanGAP Signal for Initiation of Mitosis

  • Herwig Ponstingl
  • F. Ralf Bischoff
Conference paper
Part of the NATO ASI Series book series (volume 72)


In most eukaryotic cells checkpoints ensure that DNA replication is completed before the onset of mitosis. Experimentally these controls can be overrun, e.g., by fusion of S-phase cells with mitotic cells (Johnson and Rao, 1970), by adding 5 mM caffeine (Schlegel and Pardee, 1986) to the medium of S-phase cells, or by okadaic acid (Yamashita et al., 1990), resulting in premature condensation of the chromosomes and in their ‘pulverized’ appearance under the microscope.


Okadaic Acid Chromosome Condensation Premature Chromosome Condensation Mitotic Control p34Cdc2 Kinase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aebi M, Clark MW, Vijayraghavan U, Abelson J (1990) A yeast mutant, PRP20, altered in mRNA metabolism and maintenance of the nuclear structure, is defective in a gene homologous to the human gene RCC1 which is involved in the control of chromosome condensation. Mol. Gen. Genet. 224:72–80.PubMedCrossRefGoogle Scholar
  2. Bischoff FR, Ponstingl H (1991a) Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1. Nature 354: 80–82.PubMedCrossRefGoogle Scholar
  3. Bischoff FR, Ponstingl H (1991b) Mitotic regulator protein RCC1 is complexed with a nuclear ras-related polypeptide. Proc. Natl. Acad. Sci. USA 88:10830–834.PubMedCrossRefGoogle Scholar
  4. Bischoff FR, Maier G, Tilz G, Ponstingl H (1990) A 47 kDa human nuclear protein recognized by antikinetochore autoimmune sera is homologous with the protein encoded by RCC1, a gene implicated in onset of chromosome condensation Proc. Natl. Acad. Sci. USA 87: 8617–8621.CrossRefGoogle Scholar
  5. Clark KL, Sprague Jr. GF (1989) Yeast pheromone response pathway: characterization of a suppressor that restores mating to receptorless mutants. Mol. Cell.Biol. 9:2682–2694.PubMedGoogle Scholar
  6. Dasso M, Nishitani H, Kornbluth S, Nishimoto T, Newport JW (1992) RCC1, a regulator of mitosis, is essential for DNA replication. Mol. Cell.Biol. 12: 3337–3345.PubMedGoogle Scholar
  7. Drivas GT, Shin A, Coutavas E, Rush MG, D’Eustachio P (1990). Characterization of four novel ras-like genes expressed in a human teratocarcinoma cell line. Mol. Cell. Biol. 10: 1793–1798.PubMedGoogle Scholar
  8. Frasch M (1991) The maternally expressed Drosophila gene encoding the chromatin-binding protein BJ1 is a homolog of the vertebrate gene regulator of chromatin condensation, RCC1. EMBO J. 10: 1225–1236.PubMedGoogle Scholar
  9. Gould KL, Nurse P (1989) Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis. Nature 342: 39–45.PubMedCrossRefGoogle Scholar
  10. Igarashi M, Nagata A, Jinno S, Suto K, Okayama H (1991) Wee1+-like gene in human cells. Nature 353: 80–83.PubMedCrossRefGoogle Scholar
  11. Johnson RT, Rao PN (1970) Mammalian cell fusion: Induction of premature chromosome condensation in interphase nuclei. Nature 226:717–722.PubMedCrossRefGoogle Scholar
  12. Kai R, Ohtsubo M, Sekiguchi M, Nishimoto T (1986) Molecular cloning of a human gene that regulates chromosome condensation and is essential for cell proliferation. Mol. Cell. Biol. 6: 2027–2032PubMedGoogle Scholar
  13. Kumagai A, Dunphy WG (1991) The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system. Cell 64:903–914.PubMedCrossRefGoogle Scholar
  14. Lundgren K, Walworth N, Booher R, Deminsky M, Kirschner M, Beach D (1991) Mik1 and wee1 cooperate in the inhibitory tyrosine phosphorylation of cdc2. Cell 64:1111–1122.PubMedCrossRefGoogle Scholar
  15. Martin GA, Viskochil D, Bollag G, McCabe PC, Crosier WJ, Haubruck H, Conroy L, Clark R, O’Connell P, Cawthon RM, Innis MA, McCormick F (1990) The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p21. Cell 63:843–849.PubMedCrossRefGoogle Scholar
  16. Matsumoto T, Beach D (1991) Premature initiation of mitosis in yeast lacking RCC1 or an interacting GTPase. Cell 66:347–360.PubMedCrossRefGoogle Scholar
  17. Meijer L, Azzi I, Wang JY (1991) Cyclin B targets p34cdc2 for tyrosine phosphorylation. EMBO J. 10:1545–1554.PubMedGoogle Scholar
  18. Moria AO, Draetta G, Beach D, Wang JYJ (1989) Reversible tyrosine phosphorylation of cdc2: dephosphorylation accompanies activation during entry into mitosis. Cell 58:193–203.CrossRefGoogle Scholar
  19. Nishimoto T, Eilen E, Basilico C (1978) Premature chromosome condensation in a ts DNA mutant of BHK cells. Cell 15: 475–483.PubMedCrossRefGoogle Scholar
  20. Nishimoto T, Ishida R, Ajiro K, Yamamoto S, Takahashi T (1981) The synthesis of protein(s) for chromosome condensation may be regulated by a post-transcriptional mechanism. J. Cell Physiol. 109: 299–308.PubMedCrossRefGoogle Scholar
  21. Nishitani H, Ohtsubo M, Yamashita K, Iida H, Pines J, Yasudo H, Shibata Y, Hunter T, Nishimoto T (1991) Loss of RCC1, a nuclear DNA-binding protein, uncouples the completion of DNA replication from the activation of cdc2 protein kinase and mitosis. EMBO J. 10:1555–1564.PubMedGoogle Scholar
  22. Ohtsubo M, Kai R, Furuno N, Sekiguchi T, Sekiguchi M, Hayashida H, Kuma K, Miyata T, Fukushige S, Murotsu T, Matsubara K, Nishimoto T (1987) Isolation and characterization of the active cDNA of the human cell cycle gene (RCC1) involved in the regulation of onset of chromosome condensation. Genes Dev. 1: 585–593.PubMedCrossRefGoogle Scholar
  23. Pai EF, Kabsch W, Krengel U, Holmes KC, John J, Wittinghofer A (1989) Structure of the guanine-nucleotide-binding domain of the Ha-ras oncogene product p21 in the triphosphate conformation. Nature 341: 209–214.PubMedCrossRefGoogle Scholar
  24. Russell P, Nurse P (1987) The mitotic inducer nim1+ functions in a regulatory network of protein kinase homologs controlling the initiation of mitosis. Cell 49: 569–576.PubMedCrossRefGoogle Scholar
  25. Schlegel R, Pardee AB (1986) Caffeine-induced uncoupling of mitosis from the completion of DNA replication in mammalian cells. Science 232:1264–1266.PubMedCrossRefGoogle Scholar
  26. Seino H, Hisamoto N, Uzawa S, Sekiguchi T, Nishimoto T (1992) DNA-binding domain of RCC1 protein is not essential for coupling mitosis with DNA replication. J. Cell Sci. 102: 393–400.PubMedGoogle Scholar
  27. Trahey M, Wong G, Halenbeck R, Rubinfeld B, Martin GA, Ladner M, Long CM, Crosier WJ, Watt K, Koths K, McCormick F (1988) Molecular cloning of two types of GAP complementary DNA from human placenta. Science 242:1697–1700.PubMedCrossRefGoogle Scholar
  28. Wiesmüller L, Wittinghofer A (1992) Expression of the GTPase activating domain of the neurofibromatosis type 1 (NF1) gene in Escherichia coli and role of the conserved lysine residue. J. Biol. Chem. 267: 10207–10210.PubMedGoogle Scholar
  29. Yamashita K, Yasuda H, Pines J, Yasumoto K, Nishitani H, Ohtsubo M, Hunter T, Sugimura T, Nishimoto T (1990) Okadaic acid, a potent inhibitor of type 1 and type 2A protein phosphatases, activates cdc2/Hl kinase and transiently induces a premature mitosis-like state in BHK21 cells. EMBO J. 9:4331–4339.PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • Herwig Ponstingl
    • 1
  • F. Ralf Bischoff
    • 1
  1. 1.Project Molecular Biology of MitosisDeutsches KrebsforschungszentrumHeidelbergGermany

Personalised recommendations