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PMID: 9256460 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The catalytic subunit of yeast telomerase.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 17 ·1997-08-19 ·Pages 9202-7

Counter CM, Meyerson M, Eaton EN, Weinberg RA

Abstract

Telomerase is an RNA-directed DNA polymerase, composed of RNA and protein subunits, that replicates the telomere ends of linear eukaryotic chromosomes. Using a genetic strategy described here, we identify the product of the EST2 gene, Est2p, as a subunit of telomerase in the yeast Saccharomyces cerevisiae. Est2p is required for enzyme catalysis, as mutations in EST2 were found to result in the absence of telomerase activity. Immunochemical experiments show that Est2p is an integral subunit of the telomerase enzyme. Critical catalytic residues present in RNA-directed DNA polymerases are conserved in Est2p; mutation of one such residue abolishes telomerase activity, suggesting a direct catalytic role for Est2p.

MeSH Terms
Amino Acid Sequence Base Sequence Binding Sites Molecular Sequence Data Mutagenesis, Site-Directed Saccharomyces cerevisiae/enzymology Telomerase/chemistry,genetics,metabolism
Chemicals
Telomerase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Counter C M
Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Meyerson M
Eaton E N
Weinberg R A
References (39)
39 references, click to expand
  1. Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor.
    Science. 1992 Jun 26;256(5065):1783-90 PMID: 1377403
  2. TLP1: a gene encoding a protein component of mammalian telomerase is a novel member of WD repeats family.
    Cell. 1997 Mar 21;88(6):875-84 PMID: 9118230
  3. Telomerase activity in human ovarian carcinoma.
    Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):2900-4 PMID: 8159676
  4. Large-scale analysis of gene expression, protein localization, and gene disruption in Saccharomyces cerevisiae.
    Genes Dev. 1994 May 1;8(9):1087-105 PMID: 7926789
  5. TLC1: template RNA component of Saccharomyces cerevisiae telomerase.
    Science. 1994 Oct 21;266(5184):404-9 PMID: 7545955
  6. Function and structure relationships in DNA polymerases.
    Annu Rev Biochem. 1994;63:777-822 PMID: 7526780
  7. Specific association of human telomerase activity with immortal cells and cancer.
    Science. 1994 Dec 23;266(5193):2011-5 PMID: 7605428
  8. Reverse transcriptase motifs in the catalytic subunit of telomerase.
    Science. 1997 Apr 25;276(5312):561-7 PMID: 9110970
  9. Organization of DNA sequences and replication origins at yeast telomeres.
    Cell. 1983 Jun;33(2):563-73 PMID: 6345000
  10. The molecular structure of centromeres and telomeres.
    Annu Rev Biochem. 1984;53:163-94 PMID: 6383193
  11. Genetic control of chromosome length in yeast.
    Proc Natl Acad Sci U S A. 1985 Jan;82(2):506-10 PMID: 2982162
  12. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts.
    Cell. 1985 Dec;43(2 Pt 1):405-13 PMID: 3907856
  13. Site-specific mutagenesis of AIDS virus reverse transcriptase.
    Nature. 1987 Jun 25-Jul 1;327(6124):716-7 PMID: 2439916
  14. A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis.
    Nature. 1989 Jan 26;337(6205):331-7 PMID: 2463488
  15. A mutant with a defect in telomere elongation leads to senescence in yeast.
    Cell. 1989 May 19;57(4):633-43 PMID: 2655926
  16. Identification of four conserved motifs among the RNA-dependent polymerase encoding elements.
    EMBO J. 1989 Dec 1;8(12):3867-74 PMID: 2555175
  17. Telomeres shorten during ageing of human fibroblasts.
    Nature. 1990 May 31;345(6274):458-60 PMID: 2342578
  18. Telomere reduction in human colorectal carcinoma and with ageing.
    Nature. 1990 Aug 30;346(6287):866-8 PMID: 2392154
  19. Origin and evolution of retroelements based upon their reverse transcriptase sequences.
    EMBO J. 1990 Oct;9(10):3353-62 PMID: 1698615
  20. Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity.
    EMBO J. 1992 May;11(5):1921-9 PMID: 1582420
  21. Regulatable promoters of Saccharomyces cerevisiae: comparison of transcriptional activity and their use for heterologous expression.
    Nucleic Acids Res. 1994 Dec 25;22(25):5767-8 PMID: 7838736
  22. Modulation of Saccharomyces cerevisiae DNA double-strand break repair by SRS2 and RAD51.
    Genetics. 1995 Mar;139(3):1189-99 PMID: 7768432
  23. Purification of Tetrahymena telomerase and cloning of genes encoding the two protein components of the enzyme.
    Cell. 1995 Jun 2;81(5):677-86 PMID: 7774009
  24. Telomerase in yeast.
    Science. 1995 Jul 21;269(5222):396-400 PMID: 7618104
  25. The RNA component of human telomerase.
    Science. 1995 Sep 1;269(5228):1236-41 PMID: 7544491
  26. Telomerase, cell immortality, and cancer.
    Cold Spring Harb Symp Quant Biol. 1994;59:307-15 PMID: 7587082
  27. Telomeres: beginning to understand the end.
    Science. 1995 Dec 8;270(5242):1601-7 PMID: 7502069
  28. Use of polymerase chain reaction epitope tagging for protein tagging in Saccharomyces cerevisiae.
    Yeast. 1995 Oct;11(13):1265-74 PMID: 8553697
  29. Human telomerase RNA and telomerase activity in immortal cell lines and tumor tissues.
    Cancer Res. 1996 Feb 1;56(3):645-50 PMID: 8564985
  30. Differential regulation of telomerase activity and telomerase RNA during multi-stage tumorigenesis.
    Nat Genet. 1996 Feb;12(2):200-4 PMID: 8563761
  31. Cap-prevented recombination between terminal telomeric repeat arrays (telomere CPR) maintains telomeres in Kluyveromyces lactis lacking telomerase.
    Genes Dev. 1996 Jul 15;10(14):1822-34 PMID: 8698241
  32. Cdc13p: a single-strand telomeric DNA-binding protein with a dual role in yeast telomere maintenance.
    Science. 1996 Oct 11;274(5285):249-52 PMID: 8824190
  33. Life with 6000 genes.
    Science. 1996 Oct 25;274(5287):546, 563-7 PMID: 8849441
  34. The Saccharomyces CDC13 protein is a single-strand TG1-3 telomeric DNA-binding protein in vitro that affects telomere behavior in vivo.
    Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13760-5 PMID: 8943008
  35. Senescence mutants of Saccharomyces cerevisiae with a defect in telomere replication identify three additional EST genes.
    Genetics. 1996 Dec;144(4):1399-412 PMID: 8978029
  36. Est1 has the properties of a single-stranded telomere end-binding protein.
    Genes Dev. 1996 Dec 15;10(24):3094-104 PMID: 8985179
  37. A mammalian telomerase-associated protein.
    Science. 1997 Feb 14;275(5302):973-7 PMID: 9020079
  38. Telomerase RNA mutations in Saccharomyces cerevisiae alter telomerase action and reveal nonprocessivity in vivo and in vitro.
    Genes Dev. 1997 Feb 15;11(4):528-40 PMID: 9042865
  39. Reverse transcriptase activity associated with maturase-encoding group II introns in yeast mitochondria.
    Cell. 1993 Apr 9;73(1):133-46 PMID: 7681727
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.17.9202
Published
1997-08-19
Pages
9202-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC23115
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.94.17.9202 PMC Full Text View journal details
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