Originally published as Genetics Published Articles Ahead of Print on October 9, 2008.

Genetics, Vol. 180, 2251-2266, December 2008, Copyright © 2008
doi:10.1534/genetics.108.092577

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

S. G. Addinall^*, M. Downey^,, M. Yu^*, M. K. Zubko^*,1, J. Dewar^*, A. Leake^*, J. Hallinan^*,, O. Shaw^*,, K. James^*,, D. J. Wilkinson^*,**, A. Wipat^*,, D. Durocher^, and D. Lydall^*,2

^* Centre for Integrated Systems Biology of Ageing and Nutrition, Ageing Research Laboratories, Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, United Kingdom, Samuel Lunenfeld Research Institute, Toronto, Ontario M5G 1X5, Canada, Department of Molecular Genetics, University of Toronto, Ontario M5S 1A8, Canada, ^** School of Mathematics and Statistics, Newcastle University, Newcastle upon Tyne NE1 7RU, United Kingdom and School of Computing Science, Newcastle University, Newcastle upon Tyne NE1 7RU, United Kingdom

² Corresponding author: Centre for Integrated Systems Biology of Ageing and Nutrition, Ageing Research Laboratories, Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, United Kingdom.
E-mail: d.a.lydall{at}ncl.ac.uk

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.

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