Dechat T, Pfleghaar K, Sengupta K et al.Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin. Genes Dev 22:832-853

Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Genes & Development (Impact Factor: 10.8). 05/2008; 22(7):832-53. DOI: 10.1101/gad.1652708
Source: PubMed


Over the past few years it has become evident that the intermediate filament proteins, the types A and B nuclear lamins, not only provide a structural framework for the nucleus, but are also essential for many aspects of normal nuclear function. Insights into lamin-related functions have been derived from studies of the remarkably large number of disease-causing mutations in the human lamin A gene. This review provides an up-to-date overview of the functions of nuclear lamins, emphasizing their roles in epigenetics, chromatin organization, DNA replication, transcription, and DNA repair. In addition, we discuss recent evidence supporting the importance of lamins in viral infections.

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    • "Lamins directly interact with a variety of NETs and chromatin. Accordingly they have been implicated in DNA replication, chromatin organization, mechanical stabilization of the nucleus, positioning of nuclear pores and anchoring of nuclear membrane components [24]. Intriguingly, by being comprised of just intermediate filaments, this nucleoskeleton should be far more elastic, deformable, and capable of withstanding strong compression or stretch/tension forces compared to the combined cytoplasmic filament systems. "
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    ABSTRACT: The nuclear envelope is an amazing piece of engineering. On one hand it is built like a mediaeval fortress with filament systems reinforcing its membrane walls and its double membrane structure forming a lumen like a castle moat. On the other hand its structure can adapt while maintaining its integrity like a reed bending in a river. Like a fortress it has guarded drawbridges in the nuclear pore complexes, but also has other mechanical means of communication. All this is enabled largely because of the LINC complex, a multi-protein structure that connects the intermediate filament nucleoskeleton across the lumen of the double membrane nuclear envelope to multiple cytoplasmic filament systems that themselves could act simultaneously both like mediaeval buttresses and like lines on a suspension bridge. Although many details of the greater LINC structure remain to be discerned, a number of recent findings are giving clues as to how its structural organization can yield such striking dynamic yet stable properties. Combining double- and triple-helical coiled-coils, intrinsic disorder and order, tissue-specific components, and intermediate filaments enables these unique properties. Copyright © 2015. Published by Elsevier B.V.
    FEBS letters 06/2015; 589(19). DOI:10.1016/j.febslet.2015.06.011 · 3.17 Impact Factor
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    • "The nuclear lamina, a proteinaceous meshwork consisting of A-type and B-type lamins, underlies the inner nuclear membrane and is important for maintaining interphase nuclear architecture. In addition, it provides a structural scaffold for factors involved in DNA repair, replication and transcription (Burke and Stewart, 2006; Dechat et al., 2008). Mutations in the LMNA gene are responsible for a variety of human genetic disorders, collectively called the laminopathies (Burke and Stewart, 2006; Worman et al., 2010). "
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    ABSTRACT: The cell nucleus is a highly organized structure, playing an important role in gene regulation. Understanding the mechanisms that sustain this organization is therefore essential for understanding genome function. Centromeric regions (CR) of chromosomes have been known for years to adopt specific nuclear positioning patterns, but the significance of this observation is not yet completely understood. Here, using a combination of fluorescence in situ hybridization and immunochemistry on fixed human cells and high throughput imaging, we directly and quantitatively investigated the nuclear positioning of specific human CR. We observe differential attraction of individual CR toward both the nuclear border and the nucleoli, the former being enhanced in non-proliferating cells and the latter being enhanced in proliferating cells. Similar positioning patterns are observed in two different lymphoblastoid cell lines. Moreover the positioning of CR differs from that of non centromeric regions, and CR display specific orientations within chromosome territories. These results suggest the existence of not yet characterized mechanisms that drive the nuclear positioning of CR and therefore pave the way toward a better understanding of how CR affect nuclear organization. © 2015 by The American Society for Cell Biology.
    Molecular biology of the cell 05/2015; 26(13). DOI:10.1091/mbc.E14-05-1002 · 4.47 Impact Factor
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    • "Imaging using fluorescence and electron microscopy has long suggested that the nuclear lamina is composed of structurally different intermediate filamentous lamin proteins (e.g., A-type lamins A and C and B-type lamins B1 and B2) [4] and nuclear laminassociated membrane proteins (e.g., lamin associated peptides and emerins) that together form a thin shell largely confined to a narrow region underneath the nuclear envelope with a few filamentous structures extending to the intranuclear space [1] [5]. Isolated horizontal imaging sections by confocal laser scanning microscopy through the middle of the nucleus seem to confirm this impression [1] [6] [7]: nuclear lamin proteins would form a thin layer that is spatially isotropic with no apparent difference in molecular content or density between the top and bottom portions of the nucleus in adherent cells. Such isotropic distribution of nuclear lamins, without any vertical polarization, is now conventional wisdom. "
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    ABSTRACT: The nuclear lamina is a thin filamentous meshwork that provides mechanical support to the nucleus and regulates essential cellular processes such as DNA replication, chromatin organization, cell division, and differentiation. Isolated horizontal imaging using fluorescence and electron microscopy has long suggested that the nuclear lamina is composed of structurally different A-type and B-type lamin proteins and nuclear lamin-associated membrane proteins that together form a thin layer that is spatially isotropic with no apparent difference in molecular content or density between the top and bottom of the nucleus. Chromosomes are condensed differently along the radial direction from the periphery of the nucleus to the nuclear center; therefore, chromatin accessibility for gene expression is different along the nuclear radius. However, 3D confocal reconstruction reveals instead that major lamin protein lamin A/C forms an apically polarized Frisbee-like dome structure in the nucleus of adherent cells. Here we show that both A-type lamins and transcriptionally active chromatins are vertically polarized by the tension exercised by the perinuclear actin cap (or actin cap) that is composed of highly contractile actomyosin fibers organized at the apical surface of the nucleus. Mechanical coupling between actin cap and lamina through LINC (linkers of nucleoskeleton and cytoskeleton) protein complexes induces an apical distribution of transcription-active subnucleolar compartments and epigenetic markers of transcription-active genes. This study reveals that intranuclear structures, such as nuclear lamina and chromosomal architecture, are apically polarized through the extranuclear perinuclear actin cap in a wide range of somatic adherent cells. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Biomaterials 04/2015; 48. DOI:10.1016/j.biomaterials.2015.01.023 · 8.56 Impact Factor
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