Rap1 protein regulates telomere turnover in yeast.
Telomere length is maintained through a dynamic balance between addition and loss of the terminal telomeric DNA. Normal telomere length regulation requires telomerase as well as a telomeric protein-DNA complex. Previous work has provided evidence that in the budding yeasts Kluyveromyces lactis and Saccharomyces cerevisiae, the telomeric double-stranded DNA binding protein Rap1p negatively regulates telomere length, in part by nucleating, by its C-terminal tail, a higher-order DNA binding protein complex that presumably limits access of telomerase to the chromosome end. Here we show that in K. lactis, truncating the Rap1p C-terminal tail (Rap1p-DeltaC mutant) accelerates telomeric repeat turnover in the distal region of the telomere. In addition, combining the rap1-DeltaC mutation with a telomerase template mutation (ter1-kpn), which directs the addition of mutated telomeric DNA repeats to telomeres, synergistically caused an immediate loss of telomere length regulation. Capping of the unregulated telomeres of these double mutants with functionally wild-type repeats restored telomere length control. We propose that the rate of terminal telomere turnover is controlled by Rap1p specifically through its interactions with the most distal telomeric repeats.
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143-0414, USA.
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Krauskopf
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Blackburn
D004271:DNA, Fungal; D004268:DNA-Binding Proteins / Q000502:physiology*; D007716:Kluyveromyces / Q000235:genetics*; D010641:Phenotype; D029701:Saccharomyces cerevisiae Proteins; D000089804:Shelterin Complex; D016615:Telomere; D034501:Telomere-Binding Proteins; D014157:Transcription Factors
D004271:DNA, Fungal; D004268:DNA-Binding Proteins; C440829:RAP1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D014157:Transcription Factors