Rap1 protein regulates telomere turnover in yeast

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 95; no. 21; pp. 12486 - 12491
• Main Authors: Krauskopf, A. (University of California, San Francisco, CA.), Blackburn, E.H
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 13.10.1998; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences
• Subjects: ADN; Alleles; BINDING PROTEINS; Biological Sciences; Cell division; CHROMOSOME; CHROMOSOMES; CROMOSOMAS; DNA; DNA, Fungal; DNA-Binding Proteins - physiology; DOUBLE STRANDED DNA BINDING PROTEINS; Gene expression regulation; Genetic mutation; Genetics; Genomics; Kluyveromyces - genetics; Kluyveromyces lactis; KLUYVEROMYCES MARXIANUS; KLUYVEROMYCES MARXIANUS VAR. LACTIS; LARGURA; LENGTH; LONGUEUR; MUTACION; MUTANT; MUTANTES; MUTANTS; MUTATION; Phenotype; PROTEINAS AGLUTINANTES; PROTEINE DE LIAISON; Proteins; REGULATION; REPETITIVE DNA; RNA; Saccharomyces cerevisiae Proteins; Telomere; Telomere-Binding Proteins; Telomeres; TELOMERIC REPEATS; Transcription Factors; Truncation; Yeast; Yeasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.95.21.12486

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 Saccharotnyces cerevisiae, the telomeric double-stranded DNA binding protein Rap1p negatively regulates telomere length, in part by nucleating, hy 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-delta C mutant) accelerates telomeric repeat turnover in the distal region of the telomere. In addition, combining the rap1-delta C 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