Nuclear pore complexes in the organization of silent telomeric chromatin

• Published in: Nature (London) 2000-01, Vol.403 (6765), p.108-112
• Main Authors: Nehrbass, Ulf, Galy, Vincent, Olivo-Marin, Jean-Christophe, Scherthan, Harry, Doye, Valerie, Rascalou, Nadia
• Format: Article
• Language: English
• Subjects: Antigens, Nuclear; Biological and medical sciences; Cellular Biology; Chromatin; Chromatin - metabolism; Chromatin - physiology; Chromatin - ultrastructure; Chromatin. Chromosome; DNA Damage; DNA Helicases; DNA-Binding Proteins; DNA-Binding Proteins - physiology; Fundamental and applied biological sciences. Psychology; Fungal Proteins; Fungal Proteins - genetics; Fungal Proteins - physiology; Genes; Humanities and Social Sciences; Ku Autoantigen; letter; Life Sciences; MLP1 gene; MLP2 gene; Molecular and cellular biology; Molecular genetics; multidisciplinary; Mutation; Nuclear Envelope; Nuclear Envelope - physiology; Nuclear Envelope - ultrastructure; Nuclear Pore Complex Proteins; nuclear pore complexes; Nuclear Proteins; Nuclear Proteins - physiology; Precipitin Tests; Proteins; RNA-Binding Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Science; Science (multidisciplinary); Subcellular Processes; Telomere; Telomere - physiology; Telomere - ultrastructure; Yeast; Yeasts; Yku70 protein; Yku80 protein
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/47528

The functional regulation of chromatin is closely related to its spatial organization within the nucleus. In yeast, perinuclear chromatin domains constitute areas of transcriptional repression. These 'silent' domains are defined by the presence of perinuclear telomere clusters. The only protein found to be involved in the peripheral localization of telomeres is Yku70/Yku80 (ref. 5). This conserved heterodimer can bind telomeres and functions in both repair of DNA double-strand breaks and telomere maintenance. 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 TPR homologues Mlp1 and Mlp2 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, Nup145. We propose that, through these interactions, nuclear-pore complexes organize a nuclear subdomain that is intimately involved in the regulation of chromatin metabolism.