EST2/YLR318W Summary Help

Standard Name EST2 1
Systematic Name YLR318W
Feature Type ORF, Verified
Description Reverse transcriptase subunit of the telomerase holoenzyme; essential for telomerase core catalytic activity, involved in other aspects of telomerase assembly and function; mutations in human homolog are associated with aplastic anemia (2, 3, 4 and see Summary Paragraph)
Also known as: TERT
Name Description Ever Shorter Telomeres 1
Chromosomal Location
ChrXII:766542 to 769196 | ORF Map | GBrowse
Gene Ontology Annotations All EST2 GO evidence and references
  View Computational GO annotations for EST2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 1 genes
Classical genetics
Large-scale survey
79 total interaction(s) for 39 unique genes/features.
Physical Interactions
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 10
  • Co-localization: 1
  • Reconstituted Complex: 1
  • Two-hybrid: 1

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Rescue: 5
  • Phenotypic Enhancement: 19
  • Phenotypic Suppression: 5
  • Synthetic Growth Defect: 13
  • Synthetic Lethality: 11
  • Synthetic Rescue: 11

Expression Summary
Length (a.a.) 884
Molecular Weight (Da) 102,635
Isoelectric Point (pI) 9.68
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXII:766542 to 769196 | ORF Map | GBrowse
Last Update Coordinates: 2004-02-05 | Sequence: 2011-02-03
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..2655 766542..769196 2004-02-05 2011-02-03
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000004310

Telomerase is a ribonucleoprotein complex that is essential for maintenance of telomeres, special sequences which terminate the ends of linear chromosomes. Telomerase is a reverse transcriptase that elongates the single-stranded G-rich 3' protruding ends of chromosomal DNA using an RNA molecule that is part of the telomerase complex. The extended strand provides a template for synthesis of the lagging strand by DNA polymerase, thus preventing the otherwise inevitable loss of terminal DNA at each round of replication.

In yeast, five gene products are required for telomerase activity in vivo: Est2p (the catalytic reverse transcriptase subunit), TLC1 (the template RNA), Est1p, Est3p and Cdc13p. Mutations in any of these five genes lead to progressive telomere shortening, the so-called ever shorter telomeres (EST) phenotype, followed by cell death. CDC13 is the only essential gene among the EST genes. Est2p and TLC1 form the catalytic core of telomerase, while Est1p, Est3p and Cdc13p which are dispensable for in vitro telomerase catalytic activity, play regulatory roles (5, 6, 7, 8, 9 and references therein). Cdc13p, a single stranded DNA binding protein required for telomere maintenance and elongation, binds to Est1p and this interaction is necessary for recruiting telomerase to the chromosomal ends. Est1p, Est2p and Est3p all bind to the TLC1 RNA template and Est1p also binds to 3' ends of single stranded DNA. Est1p forms a stable complex with TLC1 in the absence of Est2p or Est3p while association of Est3p with the enzyme requires an intact catalytic core. Est1p and Est3p are stable components of the telomerase holoenzyme (8).

Although Est2p is associated with telomeres during late G1 and early S phase and telomerase activity can be detected throughout the cell cycle, telomere elongation is restricted to late S phase (10), suggesting that telomerase activity is regulated by the cell-cycle machinery. It has been proposed that Est1p, whose abundance is cell-cycle regulated, plays a role in activating Est2p during late S phase. In this model, Est1p binds to the TLC1 RNA of the Est2p-TLC1 core complex and then interacts with Cdc13p to convert the inactive telomere-bound Est2p to an active form (11, 12, 10, 11, 8). The telomerase recruitment step is regulated by the yeast ku heterodimer (Yku70p-Yku80p), and Stn1p which impart positive and negative control on the Cdc13p-Est1p interaction (9, 13). The telomere elongation activity is regulated, to avoid unlimited elongation of the telomere ends by a negative feedback mechanism that inhibits telomerase activity when shortened telomeres return to their equilibrium length. This negative feedback is mediated by a protein counting mechanism that can count the precise number of Rap1p molecules bound to a telomere (14, 15).

Est2p is a homolog of p123, a telomerase protein, from the ciliated protozoan Euplotes aediculatus, which contains reverse transcriptase (RT) motifs. EST2 and p123 represent a new class of reverse transcriptase related to group II introns and non Long-terminal-repeat retrotransposons, and not related to RTs from retroviruses. Single amino acid substitutions within the reverse transcriptase motifs of Est2 protein lead to telomere shortening and senescence in yeast, indicating that these motifs are important for catalysis (6, 16, 17). Homologues of Est2p have been identified in human and S. pombe (7).

In humans, telomere length is linked to aging and cancer: in human germline cells telomeres are long, whereas in cells of somatic tissues, telomerase activity is absent and the telomeres are short. Upon sufficient shortening, the somatic cells stop dividing and become senescent. Inappropriate telomerase activity is detected in most malignant tumors, and the genes required for telomerase activity are potential targets for cancer therapy (18, 6).

Human orthologs for four of the telomerase subunits are known. Est2p, the telomerase reverse transcriptase catalytic enzyme, is similar to TERT (OMIM), TLC1, the template RNA is similar to TERC/hTR (OMIM), while Cdc13p shares sequence similarity with human POT1 (OMIM) (4, 7). There are three Est1p like proteins in humans, although only hEST1A and hEST1B have been shown to be associated with the telomerase (19). A human ortholog for EST3 hasn't been identified. Mutations in TERT (OMIM) and TERC/hTR (OMIM) cause short telomeres and congenital aplastic anemia (OMIM, 4).

Last updated: 2007-06-07 Contact SGD

References cited on this page View Complete Literature Guide for EST2
1) Lendvay TS, et al.  (1996) Senescence mutants of Saccharomyces cerevisiae with a defect in telomere replication identify three additional EST genes. Genetics 144(4):1399-412
2) Lingner J, et al.  (1997) Three Ever Shorter Telomere (EST) genes are dispensable for in vitro yeast telomerase activity. Proc Natl Acad Sci U S A 94(21):11190-5
3) Livengood AJ, et al.  (2002) Essential regions of Saccharomyces cerevisiae telomerase RNA: separate elements for Est1p and Est2p interaction. Mol Cell Biol 22(7):2366-74
4) Yamaguchi H, et al.  (2005) Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. N Engl J Med 352(14):1413-24
5) Zakian VA  (1996) Structure, function, and replication of Saccharomyces cerevisiae telomeres. Annu Rev Genet 30:141-72
6) Lowell JE and Pillus L  (1998) Telomere tales: chromatin, telomerase and telomere function in Saccharomyces cerevisiae. Cell Mol Life Sci 54(1):32-49
7) Smogorzewska A and de Lange T  (2004) Regulation of telomerase by telomeric proteins. Annu Rev Biochem 73:177-208
8) Taggart AK and Zakian VA  (2003) Telomerase: what are the Est proteins doing? Curr Opin Cell Biol 15(3):275-80
9) Dubrana K, et al.  (2001) Turning telomeres off and on. Curr Opin Cell Biol 13(3):281-9
10) Marcand S, et al.  (2000) Cell cycle restriction of telomere elongation. Curr Biol 10(8):487-90
11) Taggart AK, et al.  (2002) Est1p as a cell cycle-regulated activator of telomere-bound telomerase. Science 297(5583):1023-6
12) Diede SJ and Gottschling DE  (1999) Telomerase-mediated telomere addition in vivo requires DNA primase and DNA polymerases alpha and delta. Cell 99(7):723-33
13) Grandin N, et al.  (2000) Cdc13 cooperates with the yeast Ku proteins and Stn1 to regulate telomerase recruitment. Mol Cell Biol 20(22):8397-408
14) Ray A and Runge KW  (1999) The yeast telomere length counting machinery is sensitive to sequences at the telomere-nontelomere junction. Mol Cell Biol 19(1):31-45
15) Marcand S, et al.  (1999) Progressive cis-inhibition of telomerase upon telomere elongation. EMBO J 18(12):3509-19
16) Counter CM, et al.  (1997) The catalytic subunit of yeast telomerase. Proc Natl Acad Sci U S A 94(17):9202-7
17) Lingner J, et al.  (1997) Reverse transcriptase motifs in the catalytic subunit of telomerase. Science 276(5312):561-7
18) Barinaga M  (1997) The telomerase picture fills in. Science 276(5312):528-9
19) Lundblad V  (2003) Telomere replication: an Est fest. Curr Biol 13(11):R439-41