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Genetics, Vol. 168, 103-115, September 2004, Copyright © 2004
doi:10.1534/genetics.104.027904

Exo1 and Rad24 Differentially Regulate Generation of ssDNA at Telomeres of Saccharomyces cerevisiae cdc13-1 Mutants

Mikhajlo K. Zubko*, Sandrine Guillard{dagger} and David Lydall*,1

* School of Clinical Medical Sciences—Gerontology, University of Newcastle, Henry Wellcome Laboratory for Biogerontology Research, Newcastle upon Tyne, NE4 6BE, United Kingdom
{dagger} Cancer Research United Kingdom—Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey, SM2 5NG, United Kingdom

1 Corresponding author: School of Clinical Medical Sciences—Gerontology, University of Newcastle, Henry Wellcome Laboratory for Biogerontology Research, Institute for Ageing and Health, Newcastle upon Tyne, NE4 6BE, United Kingdom.
E-mail: d.a.lydall{at}ncl.ac.uk

Cell cycle arrest in response to DNA damage depends upon coordinated interactions between DNA repair and checkpoint pathways. Here we examine the role of DNA repair and checkpoint genes in responding to unprotected telomeres in budding yeast cdc13-1 mutants. We show that Exo1 is unique among the repair genes tested because like Rad9 and Rad24 checkpoint proteins, Exo1 inhibits the growth of cdc13-1 mutants at the semipermissive temperatures. In contrast Mre11, Rad50, Xrs2, and Rad27 contribute to the vitality of cdc13-1 strains grown at permissive temperatures, while Din7, Msh2, Nuc1, Rad2, Rad52, and Yen1 show no effect. Exo1 is not required for cell cycle arrest of cdc13-1 mutants at 36° but is required to maintain arrest. Exo1 affects but is not essential for the production of ssDNA in subtelomeric Y' repeats of cdc13-1 mutants. However, Exo1 is critical for generating ssDNA in subtelomeric X repeats and internal single-copy sequences. Surprisingly, and in contrast to Rad24, Exo1 is not essential to generate ssDNA in X or single-copy sequences in cdc13-1 rad9{Delta} mutants. We conclude that Rad24 and Exo1 regulate nucleases with different properties at uncapped telomeres and propose a model to explain our findings.




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