Open Access
Open access
eLife, volume 3

Identification of human TERT elements necessary for telomerase recruitment to telomeres

Schmidt Jens C 1
Dalby Andrew B 1
Cech Thomas R 1
1
 
Department of Chemistry and Biochemistry, BioFrontiers Institute, Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, United States
Publication typeJournal Article
Publication date2014-10-01
Journal: eLife
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor7.7
ISSN2050084X
PubMed ID:  25271372
General Biochemistry, Genetics and Molecular Biology
General Medicine
General Immunology and Microbiology
General Neuroscience
Abstract
Human chromosomes terminate in telomeres, repetitive DNA sequences bound by the shelterin complex. Shelterin protects chromosome ends, prevents recognition by the DNA damage machinery, and recruits telomerase. A patch of amino acids, termed the TEL-patch, on the OB-fold domain of the shelterin component TPP1 is essential to recruit telomerase to telomeres. In contrast, the site on telomerase that interacts with the TPP1 OB-fold is not well defined. In this study, we identify separation-of-function mutations in the TEN-domain of human telomerase reverse transcriptase (hTERT) that disrupt the interaction of telomerase with TPP1 in vivo and in vitro but have very little effect on the catalytic activity of telomerase. Suppression of a TEN-domain mutation with a compensatory charge-swap mutation in the TEL-patch indicates that their association is direct. Our findings define the interaction interface required for telomerase recruitment to telomeres, an important step towards developing modulators of this interaction as therapeutics for human disease. DOI: http://dx.doi.org/10.7554/eLife.03563.001

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GOST Copy
Schmidt J. C., Dalby A. B., Cech T. R. Identification of human TERT elements necessary for telomerase recruitment to telomeres // eLife. 2014. Vol. 3.
GOST all authors (up to 50) Copy
Schmidt J. C., Dalby A. B., Cech T. R. Identification of human TERT elements necessary for telomerase recruitment to telomeres // eLife. 2014. Vol. 3.
RIS |
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RIS Copy
TY - JOUR
DO - 10.7554/eLife.03563
UR - https://doi.org/10.7554%2FeLife.03563
TI - Identification of human TERT elements necessary for telomerase recruitment to telomeres
T2 - eLife
AU - Schmidt, Jens C
AU - Dalby, Andrew B
AU - Cech, Thomas R
PY - 2014
DA - 2014/10/01 00:00:00
PB - eLife Sciences Publications
VL - 3
PMID - 25271372
SN - 2050-084X
ER -
BibTex
Cite this
BibTex Copy
@article{2014_Schmidt
author = {Jens C Schmidt and Andrew B Dalby and Thomas R Cech},
title = {Identification of human TERT elements necessary for telomerase recruitment to telomeres},
journal = {eLife},
year = {2014},
volume = {3},
publisher = {eLife Sciences Publications},
month = {oct},
url = {https://doi.org/10.7554%2FeLife.03563},
doi = {10.7554/eLife.03563}
}
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