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A Genome-wide Suppressor and Enhancer Analysis of cdc13-1 Reveals Varied Cellular Processes Influencing Telomere Capping in Saccharomyces cerevisiae

Lookup NU author(s): Dr Stephen Addinall, Dawn Downey, Dr Min Yu, Dr Mikhajlo Zubko, James Dewar, Alan Leake, Dr Jennifer Hallinan, Dr Oliver Shaw, Dr Katherine James, Professor Darren Wilkinson, Professor Anil Wipat, Professor David Lydall

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Abstract

In Saccharomyces cerevisiae, Cdc13 binds telomeric DNA to recruit telomerase and to "cap" chromosome ends. In temperature-sensitive cdc13-1 mutants telomeric DNA is degraded and cell-cycle progression is inhibited. To identify novel proteins and pathways that cap telomeres, or that respond to uncapped telomeres, we combined cdc13-1 with the yeast gene deletion collection and used high-throughput spot-test assays to measure growth. We identified 369 gene deletions, in eight different phenotypic classes, that reproducibly demonstrated subtle genetic interactions with the cdc13-1 mutation. As expected, we identified DNA damage checkpoint, nonsense-mediated decay and telomerase components in our screen. However, we also identified genes affecting casein kinase II activity, cell polarity, mRNA degradation, mitochondrial function, phosphate transport, iron transport, protein degradation, and other functions. We also identified a number of genes of previously unknown function that we term RTC, for restriction of telomere capping, or MTC, for maintenance of telomere capping. It seems likely that many of the newly identified pathways/processes that affect growth of budding yeast cdc13-1 mutants will play evolutionarily conserved roles at telomeres. The high-throughput spot-testing approach that we describe is generally applicable and could aid in understanding other aspects of eukaryotic cell biology.


Publication metadata

Author(s): Addinall SG, Downey M, Yu M, Zubko MK, Dewar J, Leake A, Hallinan J, Shaw O, James K, Wilkinson DJ, Wipat A, Durocher D, Lydall DA

Publication type: Article

Journal: Genetics

Year: 2008

Volume: 180

Issue: 4

Pages: 2251-2266

ISSN (print): 0016-6731

ISSN (electronic): 1943-2631

Publisher: Genetics Society of America

URL: http://dx.doi.org/10.1534/genetics.108.092577

DOI: 10.1534/genetics.108.092577


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