At the end of mitosis, eukaryotic cells must segregate the two copies of their replicated genome into two new nuclear compartments. They do this either by first dismantling and later reassembling the nuclear envelope in an 'open mitosis' or by reshaping an intact nucleus and then dividing it into two in a 'closed mitosis'. Mitosis has been studied in a wide variety of eukaryotes for more than a century, but how the double membrane of the nuclear envelope is split into two at the end of a closed mitosis without compromising the impermeability of the nuclear compartment remains unknown. Here, using the fission yeast Schizosaccharomyces pombe (a classical model for closed mitosis), genetics, live-cell imaging and electron tomography, we show that nuclear fission is achieved via local disassembly of nuclear pores within the narrow bridge that links segregating daughter nuclei. In doing so, we identify the protein Les1, which is localized to the inner nuclear envelope and restricts the process of local nuclear envelope breakdown to the bridge midzone to prevent the leakage of material from daughter nuclei. The mechanism of local nuclear envelope breakdown in a closed mitosis therefore closely mirrors nuclear envelope breakdown in open mitosis, revealing an unexpectedly high conservation of nuclear remodelling mechanisms across diverse eukaryotes.
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http://dx.doi.org/10.1038/s41586-020-2648-3 | DOI Listing |
The nuclear pore complex (NPC), a multisubunit complex located within the nuclear envelope, regulates RNA export and the import and export of proteins. Here we address the role of the NPC in driving thermal stress-induced 3D genome repositioning of ( ) genes in yeast. We found that two nuclear basket proteins, Mlp1 and Nup2, although dispensable for NPC integrity, are required for driving genes into coalesced chromatin clusters, consistent with their strong, heat shock-dependent recruitment to gene regulatory and coding regions.
View Article and Find Full Text PDFThe cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction.
View Article and Find Full Text PDFMechanical properties of the nucleus are remodeled not only by extracellular forces transmitted to the nucleus but also by internal modifications, such as those induced by viral infections. During herpes simplex virus type 1 infection, the viral regulation of essential nuclear functions and growth of the nuclear viral replication compartments are known to reorganize nuclear structures. However, little is known about how this infection-induced nuclear deformation changes nuclear mechanobiology.
View Article and Find Full Text PDFCell Rep
January 2025
Genetics and Epigenetics Program, University of Texas MD Anderson Cancer Center and The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA; Department of Genetics, University of Texas MD Anderson Cancer Center and The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA. Electronic address:
ERK activity oscillates between sustained activation during oocyte formation and transient inactivation during oocyte maturation, fertilization, and early embryogenesis. Consequences of ectopic ERK activity upon oocyte maturation and in early embryogenesis are unknown. We show, in Caenorhabditis elegans, that ectopic ERK activity upon oocyte maturation (metaphase I oocytes) results in embryos with abnormalities in nuclear divisions leading to embryonic death.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
January 2025
Department of Physics, Boise State University, Boise, Idaho, United States.
Purpose: To elucidate the mechanical properties of the bovine lens cortical membrane (CM), the nuclear membrane (NM) containing cholesterol bilayer domains (CBDs), and whole bovine lenses.
Methods: The total lipids (lipids plus cholesterol) from the cortex and nucleus of a single bovine lens were isolated using the monophasic methanol extraction method. Supported CMs and NMs were prepared from total lipids extracted from the cortex and nucleus, respectively, using a rapid solvent exchange method and probe-tip sonication, followed by the fusion of unilamellar vesicles on a flat, freshly cleaved mica surface.
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