Open Access
Open access
EMBO Journal, volume 36, issue 13, pages 1908-1927

DNA ‐binding determinants and cellular thresholds for human telomerase repeat addition processivity

Wu Robert Alexander 1
TAM JANE 1
Collins Kathleen L 1
1
 
Department of Molecular and Cell Biology University of California, Berkeley Berkeley CA USA
Publication typeJournal Article
Publication date2017-05-11
Journal: EMBO Journal
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor11.4
ISSN02614189, 14602075
General Biochemistry, Genetics and Molecular Biology
Molecular Biology
General Immunology and Microbiology
General Neuroscience
Abstract
The reverse transcriptase telomerase adds telomeric repeats to chromosome ends. Purified human telomerase catalyzes processive repeat synthesis, which could restore the full ~100 nucleotides of (T2AG3)n lost from replicated chromosome ends as a single elongation event. Processivity inhibition is proposed to be a basis of human disease, but the impacts of different levels of processivity on telomere maintenance have not been examined. Here, we delineate side chains in the telomerase active‐site cavity important for repeat addition processivity, determine how they contribute to duplex and single‐stranded DNA handling, and test the cellular consequences of partial or complete loss of repeat addition processivity for telomere maintenance. Biochemical findings oblige a new model for DNA and RNA handling dynamics in processive repeat synthesis. Biological analyses implicate repeat addition processivity as essential for telomerase function. However, telomeres can be maintained by telomerases with lower than wild‐type processivity. Furthermore, telomerases with low processivity dramatically elongate telomeres when overexpressed. These studies reveal distinct consequences of changes in telomerase repeat addition processivity and expression level on telomere elongation and length maintenance.

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Wu R. A., TAM J., Collins K. L. DNA ‐binding determinants and cellular thresholds for human telomerase repeat addition processivity // EMBO Journal. 2017. Vol. 36. No. 13. pp. 1908-1927.
GOST all authors (up to 50) Copy
Wu R. A., TAM J., Collins K. L. DNA ‐binding determinants and cellular thresholds for human telomerase repeat addition processivity // EMBO Journal. 2017. Vol. 36. No. 13. pp. 1908-1927.
RIS |
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RIS Copy
TY - JOUR
DO - 10.15252/embj.201796887
UR - https://doi.org/10.15252%2Fembj.201796887
TI - DNA ‐binding determinants and cellular thresholds for human telomerase repeat addition processivity
T2 - EMBO Journal
AU - Wu, Robert Alexander
AU - TAM, JANE
AU - Collins, Kathleen L
PY - 2017
DA - 2017/05/11 00:00:00
PB - EMBO press
SP - 1908-1927
IS - 13
VL - 36
PMID - 28495680
SN - 0261-4189
SN - 1460-2075
ER -
BibTex |
Cite this
BibTex Copy
@article{2017_Wu
author = {Robert Alexander Wu and JANE TAM and Kathleen L Collins},
title = {DNA ‐binding determinants and cellular thresholds for human telomerase repeat addition processivity},
journal = {EMBO Journal},
year = {2017},
volume = {36},
publisher = {EMBO press},
month = {may},
url = {https://doi.org/10.15252%2Fembj.201796887},
number = {13},
pages = {1908--1927},
doi = {10.15252/embj.201796887}
}
MLA
Cite this
MLA Copy
Wu, Robert Alexander, et al. “DNA ‐binding determinants and cellular thresholds for human telomerase repeat addition processivity.” EMBO Journal, vol. 36, no. 13, May. 2017, pp. 1908-1927. https://doi.org/10.15252%2Fembj.201796887.
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