Regulation of telomere length requires a conserved N-terminal domain of RiF2 in Saccharomyces cerevisiae

Hannah Kaizer, Carla J. Connelly, Kelsey Bettridge, Christopher Viggiani, Carol W Greider

Research output: Contribution to journalArticle

Abstract

The regulation of telomere length equilibrium is essential for cell growth and survival since critically short telomeres signal DNA damage and cell cycle arrest. While the broad principles of length regulation are well established, the molecular mechanism of how these steps occur is not fully understood. We mutagenized the RIF2 gene in Saccharomyces cerevisiae to understand how this protein blocks excess telomere elongation. We identified an N-terminal domain in Rif2 that is essential for length regulation, which we have termed BAT domain for Blocks Addition of Telomeres. Tethering this BAT domain to Rap1 blocked telomere elongation not only in rif2Δ mutants but also in rif1Δ and rap1C-terminal deletion mutants. Mutation of a single amino acid in the BAT domain, phenylalanine at position 8 to alanine, recapitulated the rif2Δ mutant phenotype. Substitution of F8 with tryptophan mimicked the wild-type phenylalanine, suggesting the aromatic amino acid represents a protein interaction site that is essential for telomere length regulation.

Original languageEnglish (US)
Pages (from-to)573-586
Number of pages14
JournalGenetics
Volume201
Issue number2
DOIs
StatePublished - Oct 1 2015

Fingerprint

Telomere
Saccharomyces cerevisiae
Phenylalanine
Aromatic Amino Acids
Cell Cycle Checkpoints
Tryptophan
Alanine
DNA Damage
Cell Survival
Proteins
Phenotype
Amino Acids
Mutation
Growth
Genes

Keywords

  • Length regulation
  • Rif2
  • Telomerase
  • Telomeres

ASJC Scopus subject areas

  • Genetics

Cite this

Regulation of telomere length requires a conserved N-terminal domain of RiF2 in Saccharomyces cerevisiae. / Kaizer, Hannah; Connelly, Carla J.; Bettridge, Kelsey; Viggiani, Christopher; Greider, Carol W.

In: Genetics, Vol. 201, No. 2, 01.10.2015, p. 573-586.

Research output: Contribution to journalArticle

Kaizer, Hannah ; Connelly, Carla J. ; Bettridge, Kelsey ; Viggiani, Christopher ; Greider, Carol W. / Regulation of telomere length requires a conserved N-terminal domain of RiF2 in Saccharomyces cerevisiae. In: Genetics. 2015 ; Vol. 201, No. 2. pp. 573-586.
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