EST1/YLR233C Summary Help

Standard Name EST1 1
Systematic Name YLR233C
Feature Type ORF, Verified
Description TLC1 RNA-associated factor involved in telomere length regulation; recruitment subunit of telomerase; has G-quadruplex promoting activity required for telomere elongation; possible role in activating telomere-bound Est2p-TLC1-RNA; EST1 has a paralog, EBS1, that arose from the whole genome duplication (2, 3, 4, 5 and see Summary Paragraph)
Name Description Ever Shorter Telomeres 1
Chromosomal Location
ChrXII:609524 to 607425 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All EST1 GO evidence and references
  View Computational GO annotations for EST1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 3 genes
Resources
Classical genetics
null
unspecified
Large-scale survey
null
Resources
564 total interaction(s) for 505 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 16
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 7
  • Reconstituted Complex: 6
  • Two-hybrid: 8

Genetic Interactions
  • Dosage Rescue: 4
  • Negative Genetic: 44
  • Phenotypic Enhancement: 7
  • Phenotypic Suppression: 6
  • Positive Genetic: 2
  • Synthetic Growth Defect: 449
  • Synthetic Lethality: 5
  • Synthetic Rescue: 9

Resources
Expression Summary
histogram
Resources
Length (a.a.) 699
Molecular Weight (Da) 81,799
Isoelectric Point (pI) 10.11
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXII:609524 to 607425 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..2100 609524..607425 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000004223
SUMMARY PARAGRAPH for EST1

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 (6, 7, 8, 3, 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 (3).

Est1p makes multiple contributions to the function of telomerase. It recruits the telomerase catalytic to chromosome ends by serving as a bridge between the catalytic Est2p subunit and the single-stranded DNA-binding protein Cdc13p. Est1p also binds to the TLC1 RNA subunit of telomerase and once bound, Est1p interacts with the chromosome bound Cdc13p molecules to promote an activated state of the telomere-bound Est2p-TLC1 core complex. These interactions occur during S phase of the cell cycle since the abundance of Est1p is cell cycle regulated and Est1p is associated with telomeric chromatin only in late S phase (10, 11, 12, 3). The Cdc13p-Est1p interaction is positively regulated by the yeast ku heterodimer (Yku70p-Yku80p) and negatively by Stn1p, a telomere end-binding protein (9, 12).

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 (13, 7).

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) (14, 8). There are three Est1p like proteins in humans, although only hEST1A and hEST1B have been shown to be associated with the telomerase (15). 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, 14).

Last updated: 2007-06-27 Contact SGD

References cited on this page View Complete Literature Guide for EST1
1) Lundblad V and Szostak JW  (1989) A mutant with a defect in telomere elongation leads to senescence in yeast. Cell 57(4):633-43
2) 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
3) Taggart AK and Zakian VA  (2003) Telomerase: what are the Est proteins doing? Curr Opin Cell Biol 15(3):275-80
4) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
5) Zhang ML, et al.  (2010) Yeast telomerase subunit Est1p has guanine quadruplex-promoting activity that is required for telomere elongation. Nat Struct Mol Biol 17(2):202-9
6) Zakian VA  (1996) Structure, function, and replication of Saccharomyces cerevisiae telomeres. Annu Rev Genet 30:141-72
7) Lowell JE and Pillus L  (1998) Telomere tales: chromatin, telomerase and telomere function in Saccharomyces cerevisiae. Cell Mol Life Sci 54(1):32-49
8) Smogorzewska A and de Lange T  (2004) Regulation of telomerase by telomeric proteins. Annu Rev Biochem 73:177-208
9) Dubrana K, et al.  (2001) Turning telomeres off and on. Curr Opin Cell Biol 13(3):281-9
10) Taggart AK, et al.  (2002) Est1p as a cell cycle-regulated activator of telomere-bound telomerase. Science 297(5583):1023-6
11) 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
12) Marcand S, et al.  (2000) Cell cycle restriction of telomere elongation. Curr Biol 10(8):487-90
13) Barinaga M  (1997) The telomerase picture fills in. Science 276(5312):528-9
14) 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
15) Lundblad V  (2003) Telomere replication: an Est fest. Curr Biol 13(11):R439-41