Yeast telomerase and the SUN domain protein Mps3 anchor telomeres and repress subtelomeric recombination

Heiko Schober, Helder Casimiro Ferreira, Ronique Kalck, Lutz R. Gehlen, Susan M. Gasser*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

156 Citations (Scopus)

Abstract

Telomeres form the ends of linear chromosomes and protect these ends from being recognized as DNA double-strand breaks. Telomeric sequences are maintained in most cells by telomerase, a reverse transcriptase that adds TG-rich repeats to chromosome ends. In budding yeast, telomeres are organized in clusters at the nuclear periphery by interactions that depend on components of silent chromatin and the telomerase-binding factor yeast Ku (yKu). In this study, we examined whether the subnuclear localization of telomeres affects end maintenance. A telomere anchoring pathway involving the catalytic yeast telomerase subunits Est2, Est1, and Tlc1 is shown to be necessary for the perinuclear anchoring activity of Yku80 during S phase. Additionally, we identify the conserved Sad1-UNC-84 (SUN) domain protein Mps3 as the principal membrane anchor for this pathway. Impaired interference with Mps3 anchoring through overexpression of the Mps3 N terminus in a tel1 deletion background led to a senescence phenotype and to deleterious levels of subtelomeric Y' recombination. This suggests that telomere binding to the nuclear envelope helps protect telomeric repeats from recombination. Our results provide an example of a specialized structure that requires proper spatiotemporal localization to fulfill its biological role, and identifies a novel pathway of telomere protection.

Original languageEnglish
Pages (from-to)928-938
Number of pages11
JournalGenes & Development
Volume23
Issue number8
DOIs
Publication statusPublished - 15 Apr 2009

Keywords

  • telomerase
  • Sad1/UNC-84 (SUN) homology domain
  • CAJAL BODIES
  • ATM homolog Tel1
  • Telomere protection
  • DNA-DAMAGE
  • ELONGATION
  • UBIQUITIN LIGASE
  • nuclear envelope
  • nuclear organization
  • RNA
  • BUDDING YEAST
  • SACCHAROMYCES-CEREVISIAE
  • Mps3
  • REPLICATION
  • SPINDLE POLE BODY
  • CHROMOSOME ENDS

Fingerprint

Dive into the research topics of 'Yeast telomerase and the SUN domain protein Mps3 anchor telomeres and repress subtelomeric recombination'. Together they form a unique fingerprint.

Cite this