Open Access
EMBO Journal, volume 33, issue 8, pages 921-935
Human telomerase specialization for repeat synthesis by unique handling of primer-template duplex
Publication type: Journal Article
Publication date: 2014-03-11
Journal:
EMBO Journal
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 11.4
ISSN: 02614189, 14602075
PubMed ID:
24619002
General Biochemistry, Genetics and Molecular Biology
Molecular Biology
General Immunology and Microbiology
General Neuroscience
Abstract
With eukaryotic genome replication, incomplete telomere synthesis results in chromosome shortening and eventual compromise of genome stability. Telomerase counteracts this terminal sequence loss by synthesizing telomeric repeats through repeated cycles of reverse transcription of its internal RNA template. Using human telomerase domain‐complementation assays for telomerase reverse transcriptase protein (TERT) and RNA in combination with the first direct footprinting assay for telomerase association with bound DNA, we resolve mechanisms by which TERT domains and RNA motifs direct repeat synthesis. Surprisingly, we find that product‐template hybrid is sensed in a length‐ and sequence‐dependent manner to set the template 5′ boundary. We demonstrate that the TERT N‐terminal (TEN) domain determines active‐site use of the atypically short primer‐template hybrid necessary for telomeric‐repeat synthesis. Also against expectation, we show that the remainder of TERT (the TERT ring) supports functional recognition and physical protection of single‐stranded DNA adjacent to the template hybrid. These findings establish unprecedented polymerase recognition specificities for DNA‐RNA hybrid and single‐stranded DNA and suggest a new perspective on the mechanisms of telomerase specialization for telomeric‐repeat synthesis.
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1 publication, 2.04%
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Citations by publishers
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1 publication, 2.04%
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Rockefeller University Press
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Wu R. A., Collins K. Human telomerase specialization for repeat synthesis by unique handling of primer-template duplex // EMBO Journal. 2014. Vol. 33. No. 8. pp. 921-935.
GOST all authors (up to 50)
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Wu R. A., Collins K. Human telomerase specialization for repeat synthesis by unique handling of primer-template duplex // EMBO Journal. 2014. Vol. 33. No. 8. pp. 921-935.
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RIS
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TY - JOUR
DO - 10.1002/embj.201387205
UR - https://doi.org/10.1002%2Fembj.201387205
TI - Human telomerase specialization for repeat synthesis by unique handling of primer-template duplex
T2 - EMBO Journal
AU - Wu, R A
AU - Collins, K.
PY - 2014
DA - 2014/03/11 00:00:00
PB - EMBO press
SP - 921-935
IS - 8
VL - 33
PMID - 24619002
SN - 0261-4189
SN - 1460-2075
ER -
Cite this
BibTex
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@article{2014_Wu,
author = {R A Wu and K. Collins},
title = {Human telomerase specialization for repeat synthesis by unique handling of primer-template duplex},
journal = {EMBO Journal},
year = {2014},
volume = {33},
publisher = {EMBO press},
month = {mar},
url = {https://doi.org/10.1002%2Fembj.201387205},
number = {8},
pages = {921--935},
doi = {10.1002/embj.201387205}
}
Cite this
MLA
Copy
Wu, R. A., and K. Collins. “Human telomerase specialization for repeat synthesis by unique handling of primer-template duplex.” EMBO Journal, vol. 33, no. 8, Mar. 2014, pp. 921-935. https://doi.org/10.1002%2Fembj.201387205.