EST3/YIL009C-A Summary Help

Standard Name EST3 1
Systematic Name YIL009C-A
Feature Type ORF, Verified
Description Component of the telomerase holoenzyme; involved in telomere replication (2 and see Summary Paragraph)
Name Description Ever Shorter Telomeres 1
Chromosomal Location
ChrIX:336212 to 335666 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All EST3 GO evidence and references
  View Computational GO annotations for EST3
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 5 genes
Resources
Classical genetics
null
unspecified
Large-scale survey
null
Resources
42 total interaction(s) for 25 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 1
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 2
  • Co-purification: 1
  • Reconstituted Complex: 4

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Lethality: 1
  • Dosage Rescue: 1
  • Negative Genetic: 23
  • Phenotypic Enhancement: 3
  • Phenotypic Suppression: 1
  • Positive Genetic: 1
  • Synthetic Growth Defect: 1
  • Synthetic Rescue: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 181
Molecular Weight (Da) 20,554
Isoelectric Point (pI) 6.58
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrIX:336212 to 335666 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1997-10-20
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..276 336212..335937 2011-02-03 1997-10-20
Plus 1 translational frameshift 277..277 335936..335936 2011-02-03 1997-10-20
CDS 278..547 335935..335666 2011-02-03 1997-10-20
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000006432
SUMMARY PARAGRAPH for EST3

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 (3, 4, 5, 6, 7 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 (6).

Production of the functional 181 amino-acid Est3 protein requires a programmed +1 translational frameshift. In the absence of the programmed frameshift, a truncated product of 93 amino-acids may be formed, but is not known to have any function (8).

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 (9, 4).

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) (10, 5). There are three Est1p like proteins in humans, although only hEST1A and hEST1B have been shown to be associated with the telomerase (11). 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, 10).

Last updated: 2007-06-27 Contact SGD

References cited on this page View Complete Literature Guide for EST3
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) Hughes TR, et al.  (2000) The Est3 protein is a subunit of yeast telomerase. Curr Biol 10(13):809-12
3) Zakian VA  (1996) Structure, function, and replication of Saccharomyces cerevisiae telomeres. Annu Rev Genet 30:141-72
4) Lowell JE and Pillus L  (1998) Telomere tales: chromatin, telomerase and telomere function in Saccharomyces cerevisiae. Cell Mol Life Sci 54(1):32-49
5) Smogorzewska A and de Lange T  (2004) Regulation of telomerase by telomeric proteins. Annu Rev Biochem 73:177-208
6) Taggart AK and Zakian VA  (2003) Telomerase: what are the Est proteins doing? Curr Opin Cell Biol 15(3):275-80
7) Dubrana K, et al.  (2001) Turning telomeres off and on. Curr Opin Cell Biol 13(3):281-9
8) Morris DK and Lundblad V  (1997) Programmed translational frameshifting in a gene required for yeast telomere replication. Curr Biol 7(12):969-76
9) Barinaga M  (1997) The telomerase picture fills in. Science 276(5312):528-9
10) 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
11) Lundblad V  (2003) Telomere replication: an Est fest. Curr Biol 13(11):R439-41