Telomere Length Kinetics Assay (TELKA) Sorts the Telomere Length Maintenance (tlm) Mutants into Functional Groups

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2014 Apr 15

PMID 24728996

Citations 10

Authors

Linda Rubinstein

Lior Ungar

Yaniv Harari

Vera Babin

Shay Ben-Aroya

Gabor Merenyi

Lisette Marjavaara

Andrei Chabes

Martin Kupiec

Affiliations

Soon will be listed here.

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.

Citing Articles

Control of telomere length in yeast by SUMOylated PCNA and the Elg1 PCNA unloader.

Singh P, Gazy I, Kupiec M Elife. 2023; 12.

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A comparative analysis of telomere length maintenance circuits in fission and budding yeast.

Peretz I, Kupiec M, Sharan R Front Genet. 2022; 13:1033113.

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Inactivation of folylpolyglutamate synthetase Met7 results in genome instability driven by an increased dUTP/dTTP ratio.

Schmidt T, Sharma S, Reyes G, Kolodziejczak A, Wagner T, Luke B Nucleic Acids Res. 2019; 48(1):264-277.

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Genome architecture and stability in the Saccharomyces cerevisiae knockout collection.

Puddu F, Herzog M, Selivanova A, Wang S, Zhu J, Klein-Lavi S Nature. 2019; 573(7774):416-420.

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Rnr1's role in telomere elongation cannot be replaced by Rnr3: a role beyond dNTPs?.

Maicher A, Kupiec M Curr Genet. 2017; 64(3):547-550.

PMID: 29119271 DOI: 10.1007/s00294-017-0779-3.

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