Sphingolipids regulate telomere clustering by affecting the transcription of genes involved in telomere homeostasis

J Cell Sci. 2015 Jul 15;128(14):2454-67. doi: 10.1242/jcs.164160. Epub 2015 Jun 4.

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.

Keywords: Clustering; Glycosylphosphatidylinositol; Sphingolipid; Telomere; Yeast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Fungal / genetics
  • Chromosomes, Fungal / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sphingolipids / genetics
  • Sphingolipids / metabolism*
  • Telomere / genetics
  • Telomere / metabolism*
  • Telomere Homeostasis / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Saccharomyces cerevisiae Proteins
  • Sphingolipids
  • Transcription Factors