A GTPase Cycle Coupled to the Cell Cycle
Ran/TC4, a Ras-related nuclear protein first identified in a human teratocarcinoma eDNA library, is postulated to function in conjunction with another protein, RCC1 (Regulator of Chromosomal Condensation-1), to prevent the initiation of mitosis before the completion of DNA synthesis. RCC1 is a chromatin-associated DNA-binding protein as well as a Ran/TC4-specific guanine nucleotide exchange factor. One model for the function of Ran/TC4 and RCC1 is that RCC1 monitors DNA synthesis and maintains Ran/TC4 in a GTP-bound form (Ran/TC4 •GTP) until the completion of DNA synthesis and that Ran/TC4 • GTP in turn inhibits the activation of MPF (Mitosis Promoting Factor). We are testing this model, in which a GTPase cycle is coupled to the cell cycle via MPF by ex-pressing mutant Ran/TC4 proteins in human cells, and by using a Ran/TC4 - [32P]GTP complex as a probe to isolate Ran-interacting proteins.
KeywordsNonpermissive Temperature Premature Chromosome Condensation HeLa Cell Extract GTPase Cycle tsBN2 Cell
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- Aebi, M., Clark, M.W., Viiayraghavan, U., and 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 RCCI which is involved in the control of chromosome condensation, Mol. Gen. Genet 224: 72.PubMedCrossRefGoogle Scholar
- Barbacid, M., 1987, ras genes, Annu. Rev. Biocheni. 56: 779.Google Scholar
- Belhumeur, P., Lee, A., Tam, R., DiPaolo, T., Fortin, N., and Clark, M.W., GSP1 and GSP2, genetic suppressors of the prp20-1 mutant in Sacchars, iyces cerevisiae: GTP-binding proteins involved in the maintenance of nuclear organization, Mol. Cell. Biol. 13: 2152.Google Scholar
- Bourne, H.R., Sanders, D; A., and McCormick, F., 1990, The GTPase superfamily: a conserved switch for diverse cell functions, Nature 348: 125.Google Scholar
- Dasso, M., 1993, RCC1 in the cell cycle: the regulator of chromosome condensation takes on new roles, TIES 18: 96.Google Scholar
- Drivas, G.T., Massey, R., Chang, H: Y., Rush, M.G., and D’Eustachio, P., 1991b, Ras-like genes and gene families in the mouse, Mamm. Genome 1: 112.Google Scholar
- Frasch, M., 1991, The maternally expressed Drosophila gene encoding the chromatin-binding protein Bil is a homolog of the vertebrate gene regulator of chromatin condensation, RCC1, EMBO J. 10: 1225.Google Scholar
- Nishitani, H., Ohtsubo, M., Yamashita, K., Iida, H., Pines, J., Yasudo, H., Shibata, Y., Hunter, T., and 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.PubMedGoogle Scholar
- Ohtsubo, M., Kai, R., Furuno, T., Sekiguchi, T., Sekiguchi, M., Hayashida, H., Kuma, K., Miyata, T., Fukushige, S., Murotu, T., Matsubara, K., and Nishimoto, T., 1987, Isolation and characterization of the active eDNA of the human cell cycle gene (RCCI) involved in the regulation of the onset of chromo some condensation, Genes Devel. 1: 585.PubMedCrossRefGoogle Scholar
- Seino, H., Nishitani, H., Seki, T., Hisamoto, N., Tazunoki, T., Shiraki, N., Ohtsubo, M., Yamashita, K., Sekiguchi, T., and Nishimoto, T., 1991, RCC1 is a nuclear protein required for coupling activation of cdc2 kinase with DNA synthesis and for Start of the cell cycle, CSH Symp. Quant. Biol. 56: 367.CrossRefGoogle Scholar