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Vol. 15, Issue 4, 1623-1634, April 2004

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Mutant Telomere Sequences Lead to Impaired Chromosome Separation and a Unique Checkpoint Response

Jue Lin ^*, Dana L. Smith ^*, and Elizabeth H. Blackburn 

Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94143-2200

Submitted October 16, 2003; Accepted December 8, 2003
Monitoring Editor: David Botstein

Mutation of the template region in the RNA component of telomerase can cause incorporation of mutant DNA sequences at telomeres. We made all 63 mutant sequence combinations at template positions 474–476 of the yeast telomerase RNA, TLC1. Mutants contained faithfully incorporated template mutations, as well as misincorporated sequences in telomeres, a phenotype not previously reported for Saccharomyces cerevisiae telomerase template mutants. Although growth rates and telomere profiles varied widely among the tlc1 mutants, chromosome separation and segregation were always aberrant. The mutants showed defects in sister chromatid separation at centromeres as well as telomeres, suggesting activation of a cell cycle checkpoint. Deletion of the DNA damage response genes DDC1, MEC3, or DDC2/SML1 failed to restore chromosome separation in the tlc1 template mutants. These results suggest that mutant telomere sequences elicit a checkpoint that is genetically distinct from those activated by deletion of telomerase or DNA damage.

Online version of this article contains supplementary material. Online version is available at www.molbiolcell.org.

^* These authors contributed equally to this work.

Corresponding author. E-mail address: telomer{at}itsa.ucsf.edu.

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