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Nuclear pore complexes in the organization of silent telomeric chromatin

Nature volume 403, pages 108–112 (2000)Cite this article

Abstract

The functional regulation of chromatin is closely related to its spatial organization within the nucleus. In yeast, perinuclear chromatin domains constitute areas of transcriptional repression1,2,3. These ‘silent’ domains are defined by the presence of perinuclear telomere clusters4. The only protein found to be involved in the peripheral localization of telomeres is Yku70/Yku80 (ref. 5). This conserved heterodimer6 can bind telomeres7 and functions in both repair of DNA double-strand breaks8,9,10,11 and telomere maintenance7,12,13,14,15. These findings, however, do not address the underlying structural basis of perinuclear silent domains. Here we show that nuclear-pore-complex extensions formed by the conserved TPR16,17 homologues Mlp1 and Mlp218,19 are responsible for the structural and functional organization of perinuclear chromatin. Loss of MLP2 results in a severe deficiency in the repair of double-strand breaks. Furthermore, double deletion of MLP1 and MLP2 disrupts the clustering of perinuclear telomeres and releases telomeric gene repression. These effects are probably mediated through the interaction with Yku70. Mlp2 physically tethers Yku70 to the nuclear periphery, thus forming a link between chromatin and the nuclear envelope. We show, moreover, that this structural link is docked to nuclear-pore complexes through a cleavable nucleoporin, Nup14520. We propose that, through these interactions, nuclear-pore complexes organize a nuclear subdomain that is intimately involved in the regulation of chromatin metabolism.

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Figure 1: Deletion of MLP2 leads to impairment of DNA DSB repair.
Figure 2: Mlp2 mediates the perinuclear localization of Yku70–myc.
Figure 3: Double deletion of MLP1 and MLP2 releases telomeres from their perinuclear localization and leads to de-repression of telomeric silencing.
Figure 4: Mlp1 and Mlp2 are docked to the nuclear pore complex (NPC) through the cleavable nucleoporin Nup145.

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Authors and Affiliations

  1. Laboratoire de Biologie Cellulaire du Noyau, Institut Pasteur, CNRS URA 1773, 25 rue du Docteur Roux, Paris, Cedex 15, 75724, France

    Vincent Galy, Nadia Rascalou & Ulf Nehrbass

  2. Laboratoire d'Analyse d'Images Quantitative, Institut Pasteur, CNRS URA 1947, 25 rue du Docteur Roux, Paris, Cedex 15, 75724, France

    Jean-Christophe Olivo-Marin

  3. Abt. Humanbiologie and Abt. Zellbiologie, der Universitat, Postf. 3049, Kaiserslautern, D-67653, Germany

    Harry Scherthan

  4. Institut Curie, CNRS, UMR144, 22 rue Lhomond, Paris, Cedex 05, 75248, France

    Valerie Doye

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Galy, V., Olivo-Marin, JC., Scherthan, H. et al. Nuclear pore complexes in the organization of silent telomeric chromatin. Nature 403, 108–112 (2000). https://doi.org/10.1038/47528

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