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Gene Review

EST1  -  Est1p

Saccharomyces cerevisiae S288c

Synonyms: Ever shorter telomeres protein 1, L8083.15, Telomere elongation protein EST1, YLR233C
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High impact information on EST1

  • In addition, normal telomere length can be restored by expressing a Cdc13-Est1p hybrid protein [1].
  • These findings indicate that RPA activates telomerase by loading Est1p onto telomeres during S phase [1].
  • RPA regulates telomerase action by providing Est1p access to chromosome ends [1].
  • Telomerase was not detected in extracts prepared from cells grown for approximately 30 or more cell divisions in the absence of the EST1 product, Est1p [2].
  • TLC1 RNA, which determines the sequence of telomeric DNA in vivo, was present in normal amounts in est1 delta cells [2].

Biological context of EST1

  • In Saccharomyces cerevisiae, deletion of the EST1 gene results in phenotypes identical to those displayed by a deletion of a known component of telomerase (the yeast telomerase RNA), arguing that EST1 is also critical for telomerase function [3].
  • The yeast TOP3 gene, encoding DNA topoisomerase III, and EST1 gene, encoding a putative telomerase, are shown to be abutted head-to-head on chromosome XII, with the two initiation codons separated by 258 bp [4].
  • The identification of EST1 homologs in a large variety of eukaryotes may indicate that the mechanisms of telomere extension are more conserved than anticipated previously [5].
  • Delayed senescence is seen in upfDelta cells lacking the telomerase holoenzyme components Est2p and TLC1 RNA, as well as in cells lacking the telomerase regulators Est1p and Est3p [6].
  • Sudden telomere elongation and checkpoint-mediated cell cycle arrest are also triggered in wild-type cells by overproducing a protein fusion between the telomeric binding protein Cdc13 and the telomerase-associated protein Est1 [7].

Associations of EST1 with chemical compounds

  • The GST-Est2p-Tlc1 complex was partially purified by ammonium sulphate fractionation and affinity chromatography on glutathione beads, and the partially purified telomerase did not contain the other two subunits of the telomerase holoenzyme, Est1p and Est3p [8].

Physical interactions of EST1

  • Cdc13 interacts with Est1 and DNA polymerase alpha, and cells carrying the temperature-sensitive allele cdc13-1 cannot complete telomere replication at the restrictive temperature and possess long telomeres [9].
  • The absence of Est1p and Est3p from the complex during G1 phase can be attributed to proteasome-dependent degradation of Est1p [10].
  • In vivo, overexpression of Pif1p reduces telomerase association with telomeres, whereas depleting cells of Pif1p increases the levels of telomere-bound Est1p, a telomerase subunit that is present on the telomere when telomerase is active [11].

Regulatory relationships of EST1

  • We propose that Cdc13p's interaction with Est1p promotes TG(1-3) strand lengthening by telomerase and its interaction with Pol1p promotes C(1-3)A strand resynthesis by DNA polymerase alpha [12].
  • In the presence of the up-mutations, however, the ability of the Pif1p helicase to decrease telomere length and to inhibit the association of Est1p with telomeres is impaired [13].

Other interactions of EST1


Analytical, diagnostic and therapeutic context of EST1

  • Suppression of bulged-stem mutant phenotypes by overexpression of Est1p and loss of co-immunoprecipitation of the mutant RNAs with Est1p indicated that this bulged stem is necessary for association of Est1p, a telomerase regulatory subunit [19].


  1. RPA regulates telomerase action by providing Est1p access to chromosome ends. Schramke, V., Luciano, P., Brevet, V., Guillot, S., Corda, Y., Longhese, M.P., Gilson, E., Géli, V. Nat. Genet. (2004) [Pubmed]
  2. An in vitro assay for Saccharomyces telomerase requires EST1. Lin, J.J., Zakian, V.A. Cell (1995) [Pubmed]
  3. Est1 has the properties of a single-stranded telomere end-binding protein. Virta-Pearlman, V., Morris, D.K., Lundblad, V. Genes Dev. (1996) [Pubmed]
  4. Effects of yeast DNA topoisomerase III on telomere structure. Kim, R.A., Caron, P.R., Wang, J.C. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  5. A human homolog of yeast Est1 associates with telomerase and uncaps chromosome ends when overexpressed. Reichenbach, P., Höss, M., Azzalin, C.M., Nabholz, M., Bucher, P., Lingner, J. Curr. Biol. (2003) [Pubmed]
  6. Telomere cap components influence the rate of senescence in telomerase-deficient yeast cells. Enomoto, S., Glowczewski, L., Lew-Smith, J., Berman, J.G. Mol. Cell. Biol. (2004) [Pubmed]
  7. Sudden telomere lengthening triggers a Rad53-dependent checkpoint in Saccharomyces cerevisiae. Viscardi, V., Baroni, E., Romano, M., Lucchini, G., Longhese, M.P. Mol. Biol. Cell (2003) [Pubmed]
  8. Characterization of recombinant Saccharomyces cerevisiae telomerase core enzyme purified from yeast. Liao, X.H., Zhang, M.L., Yang, C.P., Xu, L.X., Zhou, J.Q. Biochem. J. (2005) [Pubmed]
  9. STM1, a gene which encodes a guanine quadruplex binding protein, interacts with CDC13 in Saccharomyces cerevisiae. Hayashi, N., Murakami, S. Mol. Genet. Genomics (2002) [Pubmed]
  10. Proteasome-dependent degradation of Est1p regulates the cell cycle-restricted assembly of telomerase in Saccharomyces cerevisiae. Osterhage, J.L., Talley, J.M., Friedman, K.L. Nat. Struct. Mol. Biol. (2006) [Pubmed]
  11. The yeast Pif1p helicase removes telomerase from telomeric DNA. Boulé, J.B., Vega, L.R., Zakian, V.A. Nature (2005) [Pubmed]
  12. The Saccharomyces telomere-binding protein Cdc13p interacts with both the catalytic subunit of DNA polymerase alpha and the telomerase-associated est1 protein. Qi, H., Zakian, V.A. Genes Dev. (2000) [Pubmed]
  13. The finger subdomain of yeast telomerase cooperates with Pif1p to limit telomere elongation. Eugster, A., Lanzuolo, C., Bonneton, M., Luciano, P., Pollice, A., Pulitzer, J.F., Stegberg, E., Berthiau, A.S., Förstemann, K., Corda, Y., Lingner, J., Géli, V., Gilson, E. Nat. Struct. Mol. Biol. (2006) [Pubmed]
  14. Cdc13 cooperates with the yeast Ku proteins and Stn1 to regulate telomerase recruitment. Grandin, N., Damon, C., Charbonneau, M. Mol. Cell. Biol. (2000) [Pubmed]
  15. Saccharomyces cerevisiae Est3p dimerizes in vitro and dimerization contributes to efficient telomere replication in vivo. Yang, C.P., Chen, Y.B., Meng, F.L., Zhou, J.Q. Nucleic Acids Res. (2006) [Pubmed]
  16. S. cerevisiae Tel1p and Mre11p are required for normal levels of Est1p and Est2p telomere association. Goudsouzian, L.K., Tuzon, C.T., Zakian, V.A. Mol. Cell (2006) [Pubmed]
  17. The Est1 subunit of yeast telomerase binds the Tlc1 telomerase RNA. Zhou, J., Hidaka, K., Futcher, B. Mol. Cell. Biol. (2000) [Pubmed]
  18. Use of polymerase chain reaction epitope tagging for protein tagging in Saccharomyces cerevisiae. Schneider, B.L., Seufert, W., Steiner, B., Yang, Q.H., Futcher, A.B. Yeast (1995) [Pubmed]
  19. A bulged stem tethers Est1p to telomerase RNA in budding yeast. Seto, A.G., Livengood, A.J., Tzfati, Y., Blackburn, E.H., Cech, T.R. Genes Dev. (2002) [Pubmed]
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