@article{90926,
  keywords = {Models, Molecular, RNA, Protein Structure, Tertiary, Protein Binding, DNA-Binding Proteins, Protein Stability, Telomere, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Telomerase, Telomere-Binding Proteins, 14-3-3 Proteins},
  author = {Christopher Webb and Virginia Zakian},
  title = {Schizosaccharomyces pombe Ccq1 and TER1 bind the 14-3-3-like domain of Est1, which promotes and stabilizes telomerase-telomere association.},
  abstract = { The telomerase protein Est1 exists in multiple organisms, including Schizosaccharomyces pombe, humans, and Saccharomyces cerevisiae, but its function has only been closely examined in S. cerevisiae, where it is a recruiter/activator of telomerase. Here, we demonstrate that S. pombe Est1 was required for the telomere association of the telomerase holoenzyme, suggesting that it too has a recruitment role. Its association with telomeres was dependent on Trt1, the catalytic subunit, and Ccq1, a telomeric protein. Surprisingly, Est1 telomere binding was only partially dependent on TER1, the telomerase RNA, even though Est1 bound nucleotides 415-507 of TER1. A ter1-Δ415-507 strain had short telomeres and very low Est1 and Trt1 telomere association in late S phase but did not senesce. An unbiased search for mutations that reduced Est1-TER1 interaction identified mutations only in the Est1 14-3-3-like domain, a phosphoserine-binding motif, the first example of a 14-3-3-like domain with RNA-binding activity. These mutations also reduced Est1-Ccq1 binding. One such mutant prevented Est1 telomere association and caused telomere loss and slow senescence, similar to ccq1Δ. We propose that the Est1-Ccq1 interaction is critical for telomerase recruitment, while the Est1-TER1 interaction acts downstream from Ccq1-mediated recruitment to stabilize the holoenzyme at the telomere. },
  year = {2012},
  journal = {Genes Dev},
  volume = {26},
  pages = {82-91},
  month = {01/2012},
  issn = {1549-5477},
  doi = {10.1101/gad.181826.111},
  language = {eng},
}