Ccq1-Tpz1TPP1 interaction facilitates telomerase and SHREC association with telomeres in fission yeast

Mol Biol Cell. 2015 Nov 1;26(21):3857-66. doi: 10.1091/mbc.E15-07-0481. Epub 2015 Sep 9.

Abstract

Evolutionarily conserved shelterin complex is essential for telomere maintenance in the fission yeast Schizosaccharomyces pombe. Elimination of the fission yeast shelterin subunit Ccq1 causes progressive loss of telomeres due to the inability to recruit telomerase, activates the DNA damage checkpoint, and loses heterochromatin at telomere/subtelomere regions due to reduced recruitment of the heterochromatin regulator complex Snf2/histone deacetylase-containing repressor complex (SHREC). The shelterin subunit Tpz1(TPP1) directly interacts with Ccq1 through conserved C-terminal residues in Tpz1(TPP1), and tpz1 mutants that fail to interact with Ccq1 show telomere shortening, checkpoint activation, and loss of heterochromatin. While we have previously concluded that Ccq1-Tpz1(TPP1) interaction contributes to Ccq1 accumulation and telomerase recruitment based on analysis of tpz1 mutants that fail to interact with Ccq1, another study reported that loss of Ccq1-Tpz1(TPP1) interaction does not affect accumulation of Ccq1 or telomerase. Furthermore, it remained unclear whether loss of Ccq1-Tpz1(TPP1) interaction affects SHREC accumulation at telomeres. To resolve these issues, we identified and characterized a series of ccq1 mutations that disrupt Ccq1-Tpz1(TPP1) interaction. Characterization of these ccq1 mutants established that Ccq1-Tpz1(TPP1) interaction contributes to optimal binding of the Ccq1-SHREC complex, and is critical for Rad3(ATR)/Tel1(ATM)-dependent Ccq1 Thr93 phosphorylation and telomerase recruitment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / metabolism
  • Checkpoint Kinase 2 / genetics
  • DNA-Binding Proteins
  • Heterochromatin / metabolism
  • Nucleotidases / metabolism*
  • Phosphorylation
  • Protein Kinases / metabolism
  • Protein Structure, Tertiary
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Telomerase / metabolism*
  • Telomere / metabolism
  • Telomere Shortening / physiology
  • Telomere-Binding Proteins / metabolism

Substances

  • Carrier Proteins
  • Ccq1 protein, S pombe
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Heterochromatin
  • Schizosaccharomyces pombe Proteins
  • Telomere-Binding Proteins
  • Tpz1 protein, S pombe
  • Protein Kinases
  • Checkpoint Kinase 2
  • Telomerase
  • Nucleotidases
  • deoxynucleotide 3'-phosphatase