title: Mutant telomere sequences lead to impaired chromosome separation and a unique checkpoint response.
abstract: 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.
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94143-2200, USA.
authors.forename: Jue
authors.initials: J
authors.lastname: Lin
authors.forename: Dana L
authors.initials: DL
authors.lastname: Smith
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Blackburn
mesh_terms: D001483:Base Sequence; D015139:Blotting, Southern; D002455:Cell Division; D002875:Chromosomes / Q000648:ultrastructure; D003001:Cloning, Molecular; D004249:DNA Damage; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D005838:Genotype; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D012313:RNA / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D012854:Sister Chromatid Exchange; D016615:Telomere / Q000648:ultrastructure*; D013997:Time Factors
chemical_list: D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D012313:RNA; D017346:Protein Serine-Threonine Kinases; C513623:TEL1 protein, S cerevisiae