Nucleic Acids Research, Vol 26, Issue 6 1487-1494, Copyright © 1998 by Oxford University Press
NF Lue and Y Peng
A number of published studies indicate that telomerase may interact with
oligonucleotide primers in a bipartite manner, with the 3'-end of the
primer positioned at the catalytic site of the enzyme and a more 5' region
of the primer binding to a second or 'anchor' site of the enzyme. We
systematically investigated the effects of mutations in the DNA primer on
overall binding and polymerization by yeast telomerase. Our studies
indicate that there is sequence-specific interaction between telomerase and
a substantial region of the DNA primer. Mutations in the 3'-most positions
of the primer reduced polymerization, yet had little effect on overall
binding affinity. In contrast, mutations around the -20 position reduced
binding affinity but had no effect on polymerization. Most strikingly,
mutations centered around the -12 position of the DNA primer reduced
overall binding affinity but dramatically enhanced primer extension, as
well as primer cleavage. This finding suggests that reduced interaction
with the -12 region of the DNA primer can facilitate a step in the
catalytic region of yeast telomerase that leads to greater polymerization.
A tripartite model of interaction between primer and telomerase is proposed
to account for the distinct effects of mutations in different regions of
the DNA primer.
ARTICLES
Negative regulation of yeast telomerase activity through an interaction with an upstream region of the DNA primer
Department of Microbiology, W.R.Hearst Microbiology Research Center, Cornell University Medical College, 1300 York Avenue, New York, NY 10021, USA. nflue@mail.med.cornell.edu
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. C. Zappulla, J. N. Roberts, K. J. Goodrich, T. R. Cech, and D. S. Wuttke Inhibition of yeast telomerase action by the telomeric ssDNA-binding protein, Cdc13p Nucleic Acids Res., February 1, 2009; 37(2): 354 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. N. Finger and T. M. Bryan Multiple DNA-binding sites in Tetrahymena telomerase Nucleic Acids Res., March 27, 2008; 36(4): 1260 - 1272. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. A. Toogun, D. C. DeZwaan, and B. C. Freeman The Hsp90 Molecular Chaperone Modulates Multiple Telomerase Activities Mol. Cell. Biol., January 1, 2008; 28(1): 457 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Chang, M. Arneric, and J. Lingner Telomerase repeat addition processivity is increased at critically short telomeres in a Tel1-dependent manner in Saccharomyces cerevisiae Genes & Dev., October 1, 2007; 21(19): 2485 - 2494. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. F. Lue A Physical and Functional Constituent of Telomerase Anchor Site J. Biol. Chem., July 15, 2005; 280(28): 26586 - 26591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Moriarty, R. J. Ward, M. A.S. Taboski, and C. Autexier An Anchor Site-Type Defect in Human Telomerase That Disrupts Telomere Length Maintenance and Cellular Immortalization Mol. Biol. Cell, July 1, 2005; 16(7): 3152 - 3161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Oulton and L. Harrington A Human Telomerase-associated Nuclease Mol. Biol. Cell, July 1, 2004; 15(7): 3244 - 3256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Huard and C. Autexier Human telomerase catalyzes nucleolytic primer cleavage Nucleic Acids Res., April 19, 2004; 32(7): 2171 - 2180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Bosoy and N. F. Lue Yeast telomerase is capable of limited repeat addition processivity Nucleic Acids Res., January 2, 2004; 32(1): 93 - 101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. F. Lue, Y.-C. Lin, and I. S. Mian A Conserved Telomerase Motif within the Catalytic Domain of Telomerase Reverse Transcriptase Is Specifically Required for Repeat Addition Processivity Mol. Cell. Biol., December 1, 2003; 23(23): 8440 - 8449. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Singh and N. F. Lue Ever shorter telomere 1 (EST1)-dependent reverse transcription by Candida telomerase in vitro: Evidence in support of an activating function PNAS, May 13, 2003; 100(10): 5718 - 5723. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. Dahlseid, J. Lew-Smith, M. J. Lelivelt, S. Enomoto, A. Ford, M. Desruisseaux, M. McClellan, N. Lue, M. R. Culbertson, and J. Berman mRNAs Encoding Telomerase Components and Regulators Are Controlled by UPF Genes in Saccharomyces cerevisiae Eukaryot. Cell, February 1, 2003; 2(1): 134 - 142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Bosoy, Y. Peng, I. S. Mian, and N. F. Lue Conserved N-terminal Motifs of Telomerase Reverse Transcriptase Required for Ribonucleoprotein Assembly in Vivo J. Biol. Chem., January 31, 2003; 278(6): 3882 - 3890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Singh, O. Steinberg-Neifach, I. S. Mian, and N. F. Lue Analysis of Telomerase in Candida albicans: Potential Role in Telomere End Protection Eukaryot. Cell, December 1, 2002; 1(6): 967 - 977. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Gavory, M. Farrow, and S. Balasubramanian Minimum length requirement of the alignment domain of human telomerase RNA to sustain catalytic activity in vitro Nucleic Acids Res., October 15, 2002; 30(20): 4470 - 4480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hossain, S. Singh, and N. F. Lue Functional Analysis of the C-terminal Extension of Telomerase Reverse Transcriptase. A PUTATIVE "THUMB" DOMAIN J. Biol. Chem., September 20, 2002; 277(39): 36174 - 36180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Bosoy and N. F. Lue Functional Analysis of Conserved Residues in the Putative "Finger" Domain of Telomerase Reverse Transcriptase J. Biol. Chem., November 30, 2001; 276(49): 46305 - 46312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Niu, J. Xia, and N. F. Lue Characterization of the Interaction between the Nuclease and Reverse Transcriptase Activity of the Yeast Telomerase Complex Mol. Cell. Biol., September 15, 2000; 20(18): 6806 - 6815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Xia, Y. Peng, I. S. Mian, and N. F. Lue Identification of Functionally Important Domains in the N-Terminal Region of Telomerase Reverse Transcriptase Mol. Cell. Biol., July 15, 2000; 20(14): 5196 - 5207. [Abstract] [Full Text] [PDF]
|
|