The TPR-containing domain within Est1 homologs exhibits species-specific roles in telomerase interaction and telomere length homeostasis
| Autor: | Fiona E. Pryde, Catherine LeBel, Lea Harrington, Aleksandar Kostic, David C.F. Sealey |
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| Rok vydání: | 2011 |
| Předmět: |
Telomerase
Saccharomyces cerevisiae Proteins lcsh:QH426-470 Protein subunit Saccharomyces cerevisiae 03 medical and health sciences Telomerase RNA component 0302 clinical medicine Species Specificity Transcription (biology) Humans Telomerase reverse transcriptase lcsh:QH573-671 Molecular Biology 030304 developmental biology Telomere-binding protein 0303 health sciences biology lcsh:Cytology Telomere biology.organism_classification Protein Structure Tertiary lcsh:Genetics Biochemistry 030217 neurology & neurosurgery Protein Binding Research Article |
| Zdroj: | BMC Molecular Biology Sealey, D C F, Kostic, A D, LeBel, C, Pryde, F & Harrington, L 2011, ' The TPR-containing domain within Est1 homologs exhibits species-specific roles in telomerase interaction and telomere length homeostasis ', BMC Molecular Biology, vol. 12, 45 . https://doi.org/10.1186/1471-2199-12-45 BMC Molecular Biology, Vol 12, Iss 1, p 45 (2011) |
| ISSN: | 1471-2199 |
| DOI: | 10.1186/1471-2199-12-45 |
| Popis: | BackgroundThe first telomerase-associated protein (Est1) was isolated in yeast due to its essential role in telomere maintenance. The human counterparts EST1A, EST1B, and EST1C perform diverse functions in nonsense-mediated mRNA decay (NMD), telomere length homeostasis, and telomere transcription. Although Est1 and EST1A/B interact with the catalytic subunit of yeast and human telomerase (Est2 and TERT, respectively), the molecular determinants of these interactions have not been elaborated fully.ResultsTo investigate the functional conservation of the EST1 protein family, we performed protein-protein interaction mapping and structure-function analysis. The domain in hEST1A most conserved between species, containing a TPR (tricotetrapeptide repeat), was sufficient for interaction of hEST1A with multiple fragments of hTERT including the N-terminus. Two mutations within the hTERT N-terminus that perturbin vivofunction (NAAIRS92, NAAIRS122) did not affect this protein interaction. ScEst1 hybrids containing the TPR of hEST1A, hEST1B, or hEST1C were expressed in yeast strains lackingEST1, yet they failed to complement senescence. Point mutations within and outside the cognate ScEst1 TPR, chosen to disrupt a putative protein interaction surface, resulted in telomere lengthening or shortening without affecting recruitment to telomeres.ConclusionsThese results identify a domain encompassing the TPR of hEST1A as an hTERT interaction module. The TPR ofS. cerevisiaeEst1 is required for telomerase-mediated telomere length maintenance in a manner that appears separable from telomere recruitment. Discrete residues in or adjacent to the TPR of Est1 also regulate telomere length homeostasis. |
| Databáze: | OpenAIRE |
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