PMID- 24728996 OWN - NLM STAT- MEDLINE DCOM- 20140804 LR - 20211021 IS - 1362-4962 (Electronic) IS - 0305-1048 (Print) IS - 0305-1048 (Linking) VI - 42 IP - 10 DP - 2014 Jun TI - Telomere length kinetics assay (TELKA) sorts the telomere length maintenance (tlm) mutants into functional groups. PG - 6314-25 LID - 10.1093/nar/gku267 [doi] AB - 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. CI - (c) The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. FAU - Rubinstein, Linda AU - Rubinstein L AD - Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel. FAU - Ungar, Lior AU - Ungar L AD - Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel. FAU - Harari, Yaniv AU - Harari Y AD - Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel. FAU - Babin, Vera AU - Babin V AD - Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel. FAU - Ben-Aroya, Shay AU - Ben-Aroya S AD - Faculty of Life Sciences Bar-Ilan University, Ramat-Gan, Israel. FAU - Merenyi, Gabor AU - Merenyi G AD - Department of Medical Biochemistry and Biophysics and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umea University, Umea 901 87, Sweden. FAU - Marjavaara, Lisette AU - Marjavaara L AD - Department of Medical Biochemistry and Biophysics and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umea University, Umea 901 87, Sweden. FAU - Chabes, Andrei AU - Chabes A AD - Department of Medical Biochemistry and Biophysics and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umea University, Umea 901 87, Sweden. FAU - Kupiec, Martin AU - Kupiec M AD - Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel martin@post.tau.ac.il. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140411 PL - England TA - Nucleic Acids Res JT - Nucleic acids research JID - 0411011 RN - 0 (DNA-Binding Proteins) RN - 0 (Saccharomyces cerevisiae Proteins) RN - 0 (YKU70 protein, S cerevisiae) RN - 0 (high affinity DNA-binding factor, S cerevisiae) RN - EC 1.17.4.- (Ribonucleotide Reductases) RN - EC 1.17.4.- (Rnr1 protein, S cerevisiae) RN - EC 6.3.2.- (Peptide Synthases) RN - EC 6.3.2.17 (folylpolyglutamate synthetase) SB - IM MH - Blotting, Southern MH - DNA End-Joining Repair MH - DNA-Binding Proteins/genetics/metabolism MH - *Mutation MH - Peptide Synthases/genetics/metabolism MH - Ribonucleotide Reductases/metabolism MH - Saccharomyces cerevisiae Proteins/genetics/metabolism MH - Telomere Homeostasis/*genetics PMC - PMC4041441 EDAT- 2014/04/15 06:00 MHDA- 2014/08/05 06:00 PMCR- 2014/04/11 CRDT- 2014/04/15 06:00 PHST- 2014/04/15 06:00 [entrez] PHST- 2014/04/15 06:00 [pubmed] PHST- 2014/08/05 06:00 [medline] PHST- 2014/04/11 00:00 [pmc-release] AID - gku267 [pii] AID - 10.1093/nar/gku267 [doi] PST - ppublish SO - Nucleic Acids Res. 2014 Jun;42(10):6314-25. doi: 10.1093/nar/gku267. Epub 2014 Apr 11.