title: Mitotic Nuclear Envelope Breakdown and Spindle Nucleation Are Controlled by Interphase Contacts between Centromeres and the Nuclear Envelope.
abstract: Faithful genome propagation requires coordination between nuclear envelope (NE) breakdown, spindle formation, and chromosomal events. The conserved linker of nucleoskeleton and cytoskeleton (LINC) complex connects fission yeast centromeres and the centrosome, across the NE, during interphase. During meiosis, LINC connects the centrosome with telomeres rather than centromeres. We previously showed that loss of telomere-LINC contacts compromises meiotic spindle formation. Here, we define the precise events regulated by telomere-LINC contacts and address the analogous possibility that centromeres regulate mitotic spindle formation. We develop conditionally inactivated LINC complexes in which the conserved SUN-domain protein Sad1 remains stable but severs interphase centromere-LINC contacts. Strikingly, the loss of such contacts abolishes spindle formation. We pinpoint the defect to a failure in the partial NE breakdown required for centrosome insertion into the NE, a step analogous to mammalian NE breakdown. Thus, interphase chromosome-LINC contacts constitute a cell-cycle control device linking nucleoplasmic and cytoplasmic events.
authors.affiliation: Telomere Biology Section, LBMB, National Cancer Institute, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA; Telomere Biology Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK. Electronic address: alfonso.fernandezalvarez@nih.gov.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Fernández-Álvarez
authors.affiliation: Telomere Biology Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Cécile
authors.initials: C
authors.lastname: Bez
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Eileen T
authors.initials: ET
authors.lastname: O'Toole
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Morphew
authors.affiliation: Telomere Biology Section, LBMB, National Cancer Institute, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA; Telomere Biology Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK. Electronic address: julie.cooper@nih.gov.
authors.forename: Julia Promisel
authors.initials: JP
authors.lastname: Cooper
mesh_terms: D059447:Cell Cycle Checkpoints / Q000502:physiology; D002503:Centromere / Q000502:physiology; D018385:Centrosome / Q000502:physiology; D020090:Chromosome Segregation / Q000502:physiology; D016681:Genome, Fungal; D007399:Interphase / Q000502:physiology; D008938:Mitosis / Q000502:physiology; D009154:Mutation; D009685:Nuclear Envelope / Q000502:physiology*; D012568:Schizosaccharomyces / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000502:physiology; D064048:Spindle Pole Bodies / Q000502:physiology*; D016615:Telomere / Q000502:physiology
chemical_list: C093512:SAD1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins
keywords: cell cycle; centromere; centrosome; chromatin; fission yeast; meiosis; mitosis; nuclear envelope breakdown; spindle pole body; telomere