Nucleic Acids Research, 1994, Vol. 22, No. 6 893-900
© 1994
MOLECULAR BIOLOGY |
The effects of nucleoside analogs on telomerase and telomeres in Tetrahymena
Department of Microbiology and Immunology Box 0414 and Department of Biochemistry and Biophysics, The University of California - San Francisco San Francisco, CA 94143-0414, USA
* To whom correspondence should be addressed
Received February 4, 1994. Accepted February 14, 1994.
The ribonucleoproteln enzyme telomerase is a specialized type of cellular reverse transcrlptase which synthesizes one strand of telomerlc DNA, using as the template a sequence in the RNA moiety of telomerase. We analyzed the effects of various nucleoside analogs, known to be chain-terminating inhibitors of retroviral reverse transcriptases, on Tetrahymena thermophila telomerase activity in vitro.Yle also analyzed the effects of such analogs on telomere length and maintenance in vivo, and on vegetative growth and mating of Tetrahymena cells. Arabinofuranyl-guanosine triphos-phate (Ara-GTP) and ddGTP both efficiently inhibited telomerase activity in vitro, while azidothymldine triphosphate (AZT-TP), dldeoxylnosine triphosphate (ddlTP) or ddTTP were less efficient inhibitors. All of these nucleoside triphosphate analogs, however, produced analog-specific alterations of the normal banding patterns seen upon gel electrophoresis of the synthesis products of telomerase, suggesting that their chain terminating and/or competitive actions differ at different positions along the RNA template. The analogs AZT, 3'-deoxy-2',3'-dldehydrothymidine (d4T) and Ara-G in nucleoside form caused consistent and rapid telomere shortening In vegetatively growing Tetrahymena. In contrast, ddG or ddl had no effect on telomere length or cell growth rates. AZT caused growth rates and viability to decrease in a fraction of cells, while Ara-G had no such effects even after several weeks in culture. Neither AZT, Ara-G, acyclc-guanosine (Acyclo-G), ddG nor ddl had any detectable effect on cell mating, as assayed by quantitation of the efficiency of formation of progeny from mated cells. However, AZT decreased the efficiency of programmed de novo telomere addition during macronuclear development In mating cells.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  X. Liu, H. Takahashi, Y. Harada, T. Ogawara, Y. Ogimura, Y. Mizushina, M. Saneyoshi, and T. Yamaguchi 3'-Azido-2',3'-dideoxynucleoside 5'-triphosphates inhibit telomerase activity in vitro, and the corresponding nucleosides cause telomere shortening in human HL60 cells Nucleic Acids Res., December 18, 2007; 35(21): 7140 - 7149. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. C. Drosopoulos and V. R. Prasad The active site residue Valine 867 in human telomerase reverse transcriptase influences nucleotide incorporation and fidelity Nucleic Acids Res., February 28, 2007; 35(4): 1155 - 1168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Doshida, M. Ohmichi, S. Tsutsumi, J. Kawagoe, T. Takahashi, B. Du, A. Mori-Abe, T. Ohta, M. Saitoh-Sekiguchi, K. Takahashi, et al. Raloxifene Increases Proliferation and Up-regulates Telomerase Activity in Human Umbilical Vein Endothelial Cells J. Biol. Chem., August 25, 2006; 281(34): 24270 - 24278. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P. Munoz and K. Collins Biochemical properties of Trypanosoma cruzi telomerase Nucleic Acids Res., September 30, 2004; 32(17): 5214 - 5222. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kondo, N. Oue, K. Yoshida, Y. Mitani, K. Naka, H. Nakayama, and W. Yasui Expression of POT1 is Associated with Tumor Stage and Telomere Length in Gastric Carcinoma Cancer Res., January 15, 2004; 64(2): 523 - 529. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-L. Mergny, J.-F. Riou, P. Mailliet, M.-P. Teulade-Fichou, and E. Gilson Natural and pharmacological regulation of telomerase Nucleic Acids Res., February 15, 2002; 30(4): 839 - 865. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. W. Tendian and W. B. Parker Interaction of Deoxyguanosine Nucleotide Analogs with Human Telomerase Mol. Pharmacol., April 1, 2000; 57(4): 695 - 699. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. Y. Rha, E. Izbicka, R. Lawrence, K. Davidson, D. Sun, M. P. Moyer, G. D. Roodman, L. Hurley, and D. Von Hoff Effect of Telomere and Telomerase Interactive Agents on Human Tumor and Normal Cell Lines Clin. Cancer Res., March 1, 2000; 6(3): 987 - 993. [Abstract] [Full Text]
|
|
|
|
 |
|
 K. C. Wolthers, S. A. Otto, G. B. A. Wisman, S. Fleury, P. Reiss, R. W. ten Kate, A. G.J. van der Zee, and F. Miedema Normal T-Cell Telomerase Activity and Upregulation in Human Immunodeficiency Virus-1 Infection Blood, February 1, 1999; 93(3): 1011 - 1019. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Bottius, N. Bakhsis, and A. Scherf Plasmodium falciparum Telomerase: De Novo Telomere Addition to Telomeric and Nontelomeric Sequences and Role in Chromosome Healing Mol. Cell. Biol., February 1, 1998; 18(2): 919 - 925. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. Lingner, T. R. Hughes, A. Shevchenko, M. Mann, V. Lundblad, and T. R. Cech Reverse Transcriptase Motifs in the Catalytic Subunit of Telomerase Science, April 25, 1997; 276(5312): 561 - 567. [Abstract] [Full Text]
|
|
|
|
 |
|
 D Gilley, M S Lee, and E H Blackburn Altering specific telomerase RNA template residues affects active site function. Genes & Dev., September 15, 1995; 9(18): 2214 - 2226. [Abstract] [PDF]
|
|