![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
A more recent version of this article appeared on July 1, 2005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on February 23, 2005
Accepted on April 18, 2005
Departments of *Anatomy and Cell Biology and Medicine, Experimental Medicine Division, McGill University, Montréal, Quebec, Canada H3A 2B2; Lady Davis Institute for Medical Research, Montréal, Quebec, Canada H3T 1E2
Monitoring Editor: Joseph Gall
Telomerase-mediated telomeric DNA synthesis is important for eukaryotic cell immortality. Telomerase adds tracts of short telomeric repeats to DNA substrates using a unique repeat addition form of processivity. It has been proposed that repeat addition processivity is partly regulated by a telomerase reverse transcriptase (TERT)-dependent anchor site; however, anchor site-mediating residues have not been identified in any TERT. We report the characterization of an N-terminal human TERT (hTERT) RNA interaction domain 1 (RID1) mutation that caused telomerase activity defects consistent with disruption of a template-proximal anchor site, including reduced processivity on short telomeric primers, and reduced activity on substrates with nontelomeric 5' sequences, but not on primers with nontelomeric G-rich 5' sequences. This mutation was located within a subregion of RID1 previously implicated in biological telomerase functions unrelated to catalytic activity (N-DAT domain). Other N-DAT and C-terminal DAT (C-DAT) mutants and a C-terminally tagged hTERT-HA variant were defective in elongating short telomeric primers, and catalytic phenotypes of DAT variants were partially or completely rescued by increasing concentrations of DNA primers. These observations imply that RID1 and the hTERT C terminus contribute to telomerase’s affinity for its substrate, and that RID1 may form part of the human telomerase anchor site.
Present address: Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 2M9.
Address correspondence to:
Chantal Autexier (chantal.autexier{at}mcgill.ca)
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
|
|
|
|
N. F. Lue and Z. Li Modeling and structure function analysis of the putative anchor site of yeast telomerase Nucleic Acids Res., August 1, 2007; (2007) gkm531v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. D. M. Wyatt, D. A. Lobb, and T. L. Beattie Characterization of Physical and Functional Anchor Site Interactions in Human Telomerase Mol. Cell. Biol., April 15, 2007; 27(8): 3226 - 3240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Terribilini, J.-H. Lee, C. Yan, R. L. Jernigan, V. Honavar, and D. Dobbs Prediction of RNA binding sites in proteins from amino acid sequence RNA, August 1, 2006; 12(8): 1450 - 1462. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Goldkorn and E. H. Blackburn Assembly of Mutant-Template Telomerase RNA into Catalytically Active Telomerase Ribonucleoprotein That Can Act on Telomeres Is Required for Apoptosis and Cell Cycle Arrest in Human Cancer Cells Cancer Res., June 1, 2006; 66(11): 5763 - 5771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Middleman, J. Choi, A. S. Venteicher, P. Cheung, and S. E. Artandi Regulation of Cellular Immortalization and Steady-State Levels of the Telomerase Reverse Transcriptase through Its Carboxy-Terminal Domain. Mol. Cell. Biol., March 1, 2006; 26(6): 2146 - 2159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. MORIARTY, D. T. MARIE-EGYPTIENNE, and C. AUTEXIER Regulation of 5' template usage and incorporation of noncognate nucleotides by human telomerase RNA, September 1, 2005; 11(9): 1448 - 1460. [Abstract] [Full Text] [PDF]
|
|
