title: Telomere length kinetics assay (TELKA) sorts the telomere length maintenance (tlm) mutants into functional groups.
abstract: Genome-wide systematic screens in yeast have uncovered a large gene network (the telomere length maintenance network or TLM), encompassing more than 400 genes, which acts coordinatively to maintain telomere length. Identifying the genes was an important first stage; the next challenge is to decipher their mechanism of action and to organize then into functional groups or pathways. Here we present a new telomere-length measuring program, TelQuant, and a novel assay, telomere length kinetics assay, and use them to organize tlm mutants into functional classes. Our results show that a mutant defective for the relatively unknown MET7 gene has the same telomeric kinetics as mutants defective for the ribonucleotide reductase subunit Rnr1, in charge of the limiting step in dNTP synthesis, or for the Ku heterodimer, a well-established telomere complex. We confirm the epistatic relationship between the mutants and show that physical interactions exist between Rnr1 and Met7. We also show that Met7 and the Ku heterodimer affect dNTP formation, and play a role in non-homologous end joining. Thus, our telomere kinetics assay uncovers new functional groups, as well as complex genetic interactions between tlm mutants.
authors.affiliation: Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel.
authors.forename: Linda
authors.initials: L
authors.lastname: Rubinstein
authors.affiliation: Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel.
authors.forename: Lior
authors.initials: L
authors.lastname: Ungar
authors.affiliation: Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel.
authors.forename: Yaniv
authors.initials: Y
authors.lastname: Harari
authors.affiliation: Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel.
authors.forename: Vera
authors.initials: V
authors.lastname: Babin
authors.affiliation: Faculty of Life Sciences Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Shay
authors.initials: S
authors.lastname: Ben-Aroya
authors.affiliation: Department of Medical Biochemistry and Biophysics and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå 901 87, Sweden.
authors.forename: Gabor
authors.initials: G
authors.lastname: Merenyi
authors.affiliation: Department of Medical Biochemistry and Biophysics and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå 901 87, Sweden.
authors.forename: Lisette
authors.initials: L
authors.lastname: Marjavaara
authors.affiliation: Department of Medical Biochemistry and Biophysics and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå 901 87, Sweden.
authors.forename: Andrei
authors.initials: A
authors.lastname: Chabes
authors.affiliation: Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel martin@post.tau.ac.il.
authors.forename: Martin
authors.initials: M
authors.lastname: Kupiec
mesh_terms: D015139:Blotting, Southern; D059766:DNA End-Joining Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D012264:Ribonucleotide Reductases / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D059505:Telomere Homeostasis / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C520769:YKU70 protein, S cerevisiae; C081647:high affinity DNA-binding factor, S cerevisiae; D012264:Ribonucleotide Reductases; C551024:Rnr1 protein, S cerevisiae; D010453:Peptide Synthases; C023103:folylpolyglutamate synthetase
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