title: Regulation of Telomere Length Requires a Conserved N-Terminal Domain of Rif2 in Saccharomyces cerevisiae.
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.
authors: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors: Hannah
authors: H
authors: Kaizer
authors: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors: Carla J
authors: CJ
authors: Connelly
authors: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors: Kelsey
authors: K
authors: Bettridge
authors: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors: Christopher
authors: C
authors: Viggiani
authors: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 cgreider@jhmi.edu.
authors: Carol W
authors: http://orcid.org/0000-0002-5494-8126
authors: CW
authors: Greider
mesh_terms: D015825:Chromosomes, Fungal; D004249:DNA Damage / Q000235:genetics; D024101:Mitochondrial Proteins / Q000235:genetics; D009154:Mutation; D012097:Repressor Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D016615:Telomere / Q000235:genetics*; D059505:Telomere Homeostasis / Q000235:genetics*; D034501:Telomere-Binding Proteins / Q000235:genetics*; D000637:Transaminases / Q000235:genetics
chemical_list: D024101:Mitochondrial Proteins; C105362:RIF2 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D034501:Telomere-Binding Proteins; C074461:RIF1 protein, S cerevisiae; D000637:Transaminases; C101168:BAT1 protein, S cerevisiae
keywords: Rif2; length regulation; telomerase; telomeres