Overview

Discovered by Carol Greider and Liz Blackburn in 1985, telomerase is a unique ribonucleoprotein (RNP) enzyme that adds telomeric repeats to the 3' end of chromosomes to counteract the DNA degradation that occurs due to the end replication problem. The Telomerase RNP contains two essential core components, the telomerase reverse transcriptase (TERT) and the telomerase RNA (TR), along with other species-specific telomerase associated proteins. The TR component contains a template region that is complementary to the telomeric DNA sequence, while TERT contains the catalytic reverse transcriptase domain responsible for nucleotide addition. The TERT and TR components are sufficient to reconstitute activity in vitro, however a variety of species-specific proteins are necessary for telomerase function in vivo and are thus thought to be involved in the regulation and biogenesis of telomerase. Telomerase is active in immortal cells such as germline and stem cells. Telomerase activity is also found in more than 85% of tumors making it a potential drug target for cancer therapy. Moreover, mutations in telomerase genes have been associated with a multitude of diseases including aplastic anaemia, dyskeratosis congenita, and idiopathic pulmonary fibrosis.

DATABASE CONTENT

The site is divided into 5 major pages: sequences, alignments, structures, diseases, and researchers. The sequences page is further broken down into separate pages for each of the components of telomerase. Each of these pages lists information related to the component, the RNA or amino acid sequence, the genbank accession number, and a link to the record at the National Center for Biotechnology Information (NCBI). The alignments page contains multiple RNA and amino acid sequence alignments based on both sequence and structural similarities. The structures page is separated into secondary and tertiary structures with a listing of files in .pdf, .jpg, and .pdb format. The diseases page is divided into the telomerase components and contains a listing of mutations and their associated clinical phenotype seen in patients. The researchers page is a listing of telomerase researchers and their affiliation.

The sequences presented within the database were used for the construction of the alignments. These alignments were then used to construct the phylogenetic trees and the secondary structures. All referenced materials used are cited and linked to the primary papers. The database is an ongoing project and will be updated continuously. The date of the last update to the site is located in the top right corner of the screen.

NOMENCLATURE

A standard nomenclature is used throughout the online database for consistency and clarity. Homologous proteins are given a single name for simplicity. The abbreviations of TR and TERT, for the telomerase RNA and reverse transcriptase, are used for brevity.

ACKNOWLEDGEMENTS

We acknowledge support provided by nsf supported National Science Foundation (NSF).

Milestones in Telomerase Research

   
   
  Identification of telomeric DNA sequence in Tetrahymena
Blackburn et al, JMB, 1978
   
Prior
to
1985
   
  Identification of telomeric DNA in yeast
Walmsley et al, Nature,1984
  Maintenance of telomeric DNA in yeast
Shampay, Szostak and Blackburn, Nature,1984
     
   
1985
  Telomerase activity identified in Tetrahymena
Greider and Blackburrn, Cell, 1985
     
     
     
     
1986
   
     
     
     
   
1987
  Telomerase is a ribonucleoprotein
Greider and Blackburn, Cell, 1987
     
     
   
1989
  Telomerase RNA (TR) is required for telomerase activity
Greider et al, Nature,1989
  Telomerase dysfunction leads to cell senescence
Lundblad and Szostak, Cell, 1989
     
     
   
1990
  Mutated TR template sequence copied into telomeric repeat
Yu et al, Nature, 1990
  Telomere shortening linked to cellular aging
Harley, Futcher, Greider, Nature, 1990
     
     
   
1991
  Ciliate TR secondary structure determined
Romero and Blackburn, Cell, 1991
     
     
     
   
1992
  Telomere length predicts replicative capacity of cells
Allsopp et al, PNAS, 1992
     
     
   
1994
  Identification of yeast TR (TLC1)
Singer and Gottschling, Science, 1994
  Telomerase activity detected in >85% of tumors
Kim et al, Science, 1994
     
     
   
1995
  Identification of human TR
Feng et al, Science, 1995
  Identification of mouse TR
Blasco et al, Science, 1995
     
   
  Identification of Euplotes and S. cerervisiae TERT
Lingner et al, Science, 1997
1997
  Identification of S. pombe and human TERT
Nakamura et al, Science, 1997
  Telomerase KO mouse
Blasco et al, Cell, 1997
  Alternative lengthening of telomere-ALT
Bryan, Nature Medicine et al, 1997
   
  Extension of cell lifespan by introducing TERT
Bodnar et al, Science, 1998
1998
  Telomerase is essential in highly proliferative mouse organs
Lee et al, Nature, 1998
  Myc activates telomerase
Wang, G&D, 1998
     
   
1999
  Association of DKC with telomerase defects
Mitchell et al, Nature, 1999
     
     
     
   
2000
  Vertebrate TR secondary structure determined
Chen et al, Cell, 2000
     
     
   
2001
  Autosomal dominant DKC linked to hTR mutations
Vulliamy et al, Nature, 2001
  Shortest telomere is critical for chromosome stability
Hemann et al, Cell, 2001
     
     
     
2002
   
     
     
     
   
2003
  Telomerase extension inhibited by POT1 binding ssDNA
Loayza et al, Nature, 2003
     
     
     
   
2004
  Yeast TR secondary structure determined
Dandjinou et al, Curr. Biol. 2004
     
     
     
   
2005
  Telomerase stimulates proliferation of hair cells
Sarin et al, Nature, 2005
     
     
     
   
2006
  Crystal structure of TEN domain of TERT determined
Jacobs et al, Nat Struct Mol Biol, 2006
     
     
     
   
2007
  Telomerase mutations linked to Idiopathic Pulmonary Fibrosis
Armanios et al, NEJM, 2007
   
   
   
   
2008