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Gene Review

EST2  -  Est2p

Saccharomyces cerevisiae S288c

Synonyms: L8543.12, Telomerase catalytic subunit, Telomerase reverse transcriptase, YLR318W
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High impact information on EST2

  • We made a large library containing random mutations in the amino terminus of the EST2 gene, which encodes the Saccharomyces cerevisiae TERT, and selected functional alleles by their ability to rescue senescence of telomerase-negative cells [1].
  • We find that recruitment of Est2p, the catalytic subunit of telomerase, and Est1p, a telomerase accessory protein, was severely reduced in mre11Delta and tel1Delta cells [2].
  • Similarly, Est2 binding to the DSB also required the Cdc13-Est1 interaction, but not synthesis of new TG repeats at the break site [3].
  • We show that in this structure three conserved sequences interact to provide a binding site for Est2p positioned near the template [4].
  • We delineated nucleotides and base-pairings within a previously mapped central domain of the Saccharomyces cerevisiae telomerase RNA (TLC1) that are important for telomerase function and for binding to the telomerase catalytic protein Est2p [4].

Biological context of EST2

  • In fact, it is turned off concomitantly with telomeres reaching a new stable length and is partially suppressed by deletion of the telomerase EST2 gene [5].
  • A combination of DEF1 null mutation with deletion of EST2 or EST3 resulted in an accelerated senescence phenotype, suggesting that Def1p is not involved in the telomerase recruitment pathway [6].
  • Est2p, the reverse transcriptase protein subunit, and TLC1, the templating RNA, are subunits of the catalytic core of yeast telomerase [3] [4] [5] [7].
  • In contrast, the levels of Est2p and Est1p binding in late S/G2 phase, the period in the cell cycle when yeast telomerase lengthens telomeres, were indistinguishable in wild-type (WT) and mec1Delta cells [2].
  • 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 [8].

Associations of EST2 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 [9].

Other interactions of EST2

  • EST1, EST2, EST3 and TLC1 function in a single pathway for telomere replication in the yeast Saccharomyces cerevisiae [1] [2], as would be expected if these genes all encode components of the same complex [7].
  • We show that overexpression of EST2 or TLC1 in yku80 mutants does not restore efficient DNA repair, or restore normal telomere function, as measured by telomere length, single-stranded G-rich strand or transcriptional silencing [10].
  • Increased levels of STN1 together with EST2 resulted in reduced telomeric silencing like that of upf mutants [11].
  • In S. cerevisiae, mutations in genes that encode telomerase components, such as the genes EST1, EST2, EST3, and TLC1, result in the loss of telomerase activity in vivo [12].
  • S. cerevisiae Tel1p and Mre11p are required for normal levels of Est1p and Est2p telomere association [2].

Analytical, diagnostic and therapeutic context of EST2


  1. Essential functions of amino-terminal domains in the yeast telomerase catalytic subunit revealed by selection for viable mutants. Friedman, K.L., Cech, T.R. Genes Dev. (1999) [Pubmed]
  2. 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]
  3. Delivery of yeast telomerase to a DNA break depends on the recruitment functions of Cdc13 and Est1. Bianchi, A., Negrini, S., Shore, D. Mol. Cell (2004) [Pubmed]
  4. A universal telomerase RNA core structure includes structured motifs required for binding the telomerase reverse transcriptase protein. Lin, J., Ly, H., Hussain, A., Abraham, M., Pearl, S., Tzfati, Y., Parslow, T.G., Blackburn, E.H. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  5. 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]
  6. Def1p is involved in telomere maintenance in budding yeast. Chen, Y.B., Yang, C.P., Li, R.X., Zeng, R., Zhou, J.Q. J. Biol. Chem. (2005) [Pubmed]
  7. The Est3 protein is a subunit of yeast telomerase. Hughes, T.R., Evans, S.K., Weilbaecher, R.G., Lundblad, V. Curr. Biol. (2000) [Pubmed]
  8. 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]
  9. 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]
  10. Telomerase subunit overexpression suppresses telomere-specific checkpoint activation in the yeast yku80 mutant. Teo, S.H., Jackson, S.P. EMBO Rep. (2001) [Pubmed]
  11. mRNAs encoding telomerase components and regulators are controlled by UPF genes in Saccharomyces cerevisiae. Dahlseid, J.N., Lew-Smith, J., Lelivelt, M.J., Enomoto, S., Ford, A., Desruisseaux, M., McClellan, M., Lue, N., Culbertson, M.R., Berman, J. Eukaryotic Cell (2003) [Pubmed]
  12. SGS1 is required for telomere elongation in the absence of telomerase. Huang, P., Pryde, F.E., Lester, D., Maddison, R.L., Borts, R.H., Hickson, I.D., Louis, E.J. Curr. Biol. (2001) [Pubmed]
  13. A specific DNA-dependent DNA polymerase is associated with Saccharomyces cerevisiae telomerase. Petrov, A.V., Dmitriev, P.V., Sokolov, K.A., Dontsova, O.A. Biochemistry Mosc. (2001) [Pubmed]
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