Coordination of chromosome alignment and mitotic progression by the chromosome-based ran signal

Hoi Y. Li, Pin Ng Win, Chi H. Wong, Pablo A Iglesias, Yixian Zheng

Research output: Contribution to journalArticle

Abstract

Mitotic spindle assembly and chromosome segregation are controlled by the cell cycle machinery and by the guanosine triphosphatase Ran (RanGTPase). We developed a spatial model that allowed us to simulate RanGTP production with different degrees of chromosome alignment in mitosis. Aided by this model, we defined three factors that modulate mitotic RanGTP gradients and mitotic progression in somatic cells. First, the completion of chromosome alignment at the metaphase plate could generate highest local RanGTP concentrations on chromosomes that could lead to spindle checkpoint silencing and metaphase-anaphase transition. Second, the concentration of RanGTP-transport- receptor (represented by RanGTP-importin β) and its spatial distribution are very sensitive to the level of RanBP1. Reduction of RanBP1 leads to an elevated RanGTP-transport-receptor concentration throughout the cell, which disrupts spindle assembly and weakens spindle checkpoint control. Finally, chromosomal RanGTP production could be dampened by a reduction of RCC1 phosphorylation by Cdc2 in mitosis. Our spatial simulation of RanGTP production using individual chromosomes should provide means to further understand how the Ran system and the cell cycle machinery coordinately regulate mitosis.

Original languageEnglish (US)
Pages (from-to)1886-1895
Number of pages10
JournalCell cycle (Georgetown, Tex.)
Volume6
Issue number15
StatePublished - Aug 1 2007

Fingerprint

Chromosomes
Mitosis
Metaphase
Cell Cycle
Machinery
Karyopherins
M Phase Cell Cycle Checkpoints
Chromosome Segregation
Anaphase
Spindle Apparatus
Cells
Guanosine
Phosphorylation
Spatial distribution

Keywords

  • Chromosome segregation
  • Mitosis
  • RanGTP gradients
  • Spindle checkpoint

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Cite this

Coordination of chromosome alignment and mitotic progression by the chromosome-based ran signal. / Li, Hoi Y.; Win, Pin Ng; Wong, Chi H.; Iglesias, Pablo A; Zheng, Yixian.

In: Cell cycle (Georgetown, Tex.), Vol. 6, No. 15, 01.08.2007, p. 1886-1895.

Research output: Contribution to journalArticle

Li, Hoi Y. ; Win, Pin Ng ; Wong, Chi H. ; Iglesias, Pablo A ; Zheng, Yixian. / Coordination of chromosome alignment and mitotic progression by the chromosome-based ran signal. In: Cell cycle (Georgetown, Tex.). 2007 ; Vol. 6, No. 15. pp. 1886-1895.
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