title: Sphingolipids regulate telomere clustering by affecting the transcription of genes involved in telomere homeostasis.
abstract: In eukaryotic organisms, including mammals, nematodes and yeasts, the ends of chromosomes, telomeres are clustered at the nuclear periphery. Telomere clustering is assumed to be functionally important because proper organization of chromosomes is necessary for proper genome function and stability. However, the mechanisms and physiological roles of telomere clustering remain poorly understood. In this study, we demonstrate a role for sphingolipids in telomere clustering in the budding yeast Saccharomyces cerevisiae. Because abnormal sphingolipid metabolism causes downregulation of expression levels of genes involved in telomere organization, sphingolipids appear to control telomere clustering at the transcriptional level. In addition, the data presented here provide evidence that telomere clustering is required to protect chromosome ends from DNA-damage checkpoint signaling. As sphingolipids are found in all eukaryotes, we speculate that sphingolipid-based regulation of telomere clustering and the protective role of telomere clusters in maintaining genome stability might be conserved in eukaryotes.
authors.affiliation: Department of Biofunctional Science and Technology, Graduate School of Biosphere Science, Hiroshima University, Hiroshima 739-8528, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Ikeda
authors.affiliation: Department of Biofunctional Science and Technology, Graduate School of Biosphere Science, Hiroshima University, Hiroshima 739-8528, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Muneoka
authors.affiliation: Department of Biofunctional Science and Technology, Graduate School of Biosphere Science, Hiroshima University, Hiroshima 739-8528, Japan.
authors.forename: Suguru
authors.initials: S
authors.lastname: Murakami
authors.affiliation: Department of Biofunctional Science and Technology, Graduate School of Biosphere Science, Hiroshima University, Hiroshima 739-8528, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Hirota
authors.affiliation: Department of Biofunctional Science and Technology, Graduate School of Biosphere Science, Hiroshima University, Hiroshima 739-8528, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Yabuki
authors.affiliation: Department of Biofunctional Science and Technology, Graduate School of Biosphere Science, Hiroshima University, Hiroshima 739-8528, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Karashima
authors.affiliation: Department of Biofunctional Science and Technology, Graduate School of Biosphere Science, Hiroshima University, Hiroshima 739-8528, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Nakazono
authors.affiliation: Department of Biofunctional Science and Technology, Graduate School of Biosphere Science, Hiroshima University, Hiroshima 739-8528, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuruno
authors.affiliation: Institute of Molecular Biotechnology, Graz University of Technology, NAWI Graz, Petersgasse 14/2, Graz 8010, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Pichler
authors.affiliation: Laboratory of Genome Structure and Function, Institute of Molecular and Cellular Biosciences, the University of Tokyo, Tokyo 113-0032, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Shirahige
authors.affiliation: Suntory Research Center, Osaka 618-8503, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kodama
authors.affiliation: Department of Biofunctional Science and Technology, Graduate School of Biosphere Science, Hiroshima University, Hiroshima 739-8528, Japan.
authors.forename: Toshi
authors.initials: T
authors.lastname: Shimamoto
authors.affiliation: Department of Biofunctional Science and Technology, Graduate School of Biosphere Science, Hiroshima University, Hiroshima 739-8528, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Mizuta
authors.affiliation: Department of Biofunctional Science and Technology, Graduate School of Biosphere Science, Hiroshima University, Hiroshima 739-8528, Japan kfunato@hiroshima-u.ac.jp.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Funato
mesh_terms: D015825:Chromosomes, Fungal / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013107:Sphingolipids / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D059505:Telomere Homeostasis / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D013107:Sphingolipids; D014157:Transcription Factors
keywords: Clustering; Glycosylphosphatidylinositol; Sphingolipid; Telomere; Yeast