Chromosome capture by microtubules is widely accepted as the universal mechanism of spindle assembly in dividing cells. However, the observed length of spindle microtubules and computer simulations of spindle assembly predict that chromosome capture is efficient in small cells, but may fail in cells with large nuclear volumes such as animal oocytes. Here we investigate chromosome congression during the first meiotic division in starfish oocytes. We show that microtubules are not sufficient for capturing chromosomes. Instead, chromosome congression requires actin polymerization. After nuclear envelope breakdown, we observe the formation of a filamentous actin mesh in the nuclear region, and find that contraction of this network delivers chromosomes to the microtubule spindle. We show that this mechanism is essential for preventing chromosome loss and aneuploidy of the egg--a leading cause of pregnancy loss and birth defects in humans.
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http://dx.doi.org/10.1038/nature03810 | DOI Listing |
J Mol Cell Biol
January 2025
MOE Key Laboratory for Membraneless Organelles & Cellular Dynamics, School of Life Sciences, University of Science and Technology of China, Hefei 230026, China.
Nat Commun
January 2025
Volastra Therapeutics, New York, NY, USA.
Chromosome instability is a prevalent vulnerability of cancer cells that has yet to be fully exploited therapeutically. To identify genes uniquely essential to chromosomally unstable cells, we mined the Cancer Dependency Map for genes essential in tumor cells with high levels of copy number aberrations. We identify and validate KIF18A, a mitotic kinesin, as a vulnerability of chromosomally unstable cancer cells.
View Article and Find Full Text PDFBiochem Pharmacol
December 2024
Center for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. Electronic address:
The discovery of new small-molecule inhibitors is essential to enhancing our understanding of biological events at the molecular level and driving advancements in drug discovery. Mitotic inhibitors have played a crucial role in development of anticancer drugs. Beyond traditional microtubule inhibitors, various inhibitors targeting specific mitotic factors have been developed.
View Article and Find Full Text PDFGenetics
November 2024
Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, 1156 High Street Santa Cruz, CA, 95064, USA.
Chromosome congression and alignment on the metaphase plate involves lateral and microtubule plus-end interactions with the kinetochore. Here we take advantage of our ability to efficiently generate a GFP-marked acentric X chromosome fragment in Drosophila neuroblasts to identify forces acting on chromosome arms that drive congression and alignment. We find acentrics efficiently congress and align on the metaphase plate, often more rapidly than kinetochore-bearing chromosomes.
View Article and Find Full Text PDFNat Commun
November 2024
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, 08003, Spain.
Subcellular compartmentalization of metabolic enzymes establishes a unique metabolic environment that elicits specific cellular functions. Indeed, the nuclear translocation of certain metabolic enzymes is required for epigenetic regulation and gene expression control. Here, we show that the nuclear localization of the mitochondrial enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) ensures mitosis progression.
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