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Generation of GTP-bound Ran by RCC1 is required for chromatin-induced mitotic spindle formation

Author

Listed:
  • Rafael E. Carazo-Salas
  • Giulia Guarguaglini

    (CNR, Centre of Evolutionary Genetics, University "La Sapienza")

  • Oliver J. Gruss

    (EMBL)

  • Alexandra Segref

    (EMBL)

  • Eric Karsenti

    (EMBL)

  • Iain W. Mattaj

    (EMBL)

Abstract

Chromosomes are segregated by two antiparallel arrays of microtubules arranged to form the spindle apparatus. During cell division, the nucleation of cytosolic microtubules is prevented and spindle microtubules nucleate from centrosomes (in mitotic animal cells) or around chromosomes (in plants and some meiotic cells)1,2. The molecular mechanism by which chromosomes induce local microtubule nucleation in the absence of centrosomes is unknown3,4,5, but it can be studied by adding chromatin beads to Xenopus egg extracts6. The beads nucleate microtubules that eventually reorganize into a bipolar spindle. RCC1, the guanine-nucleotide-exchange factor for the GTPase protein Ran, is a component of chromatin. Using the chromatin bead assay, we show here that the activity of chromosome-associated RCC1 protein is required for spindle formation. Ran itself, when in the GTP-bound state (Ran-GTP), induces microtubule nucleation and spindle-like structures in M-phase extract. We propose thatRCC1 generates a high local concentration of Ran-GTP around chromatin which in turn induces the local nucleation of microtubules.

Suggested Citation

  • Rafael E. Carazo-Salas & Giulia Guarguaglini & Oliver J. Gruss & Alexandra Segref & Eric Karsenti & Iain W. Mattaj, 1999. "Generation of GTP-bound Ran by RCC1 is required for chromatin-induced mitotic spindle formation," Nature, Nature, vol. 400(6740), pages 178-181, July.
    • Handle: RePEc:nat:nature:v:400:y:1999:i:6740:d:10.1038_22133
    DOI: 10.1038/22133
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    Cited by:

    1. Bernardo Gouveia & Sagar U. Setru & Matthew R. King & Aaron Hamlin & Howard A. Stone & Joshua W. Shaevitz & Sabine Petry, 2023. "Acentrosomal spindles assemble from branching microtubule nucleation near chromosomes in Xenopus laevis egg extract," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Ai Kiyomitsu & Toshiya Nishimura & Shiang Jyi Hwang & Satoshi Ansai & Masato T. Kanemaki & Minoru Tanaka & Tomomi Kiyomitsu, 2024. "Ran-GTP assembles a specialized spindle structure for accurate chromosome segregation in medaka early embryos," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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