Open Access
Nucleic Acids Research, volume 42, issue 3, pages 1733-1746
Telomere extension by telomerase and ALT generates variant repeats by mechanistically distinct processes
Publication type: Journal Article
Publication date: 2013-11-12
Journal:
Nucleic Acids Research
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 14.9
ISSN: 03051048, 13624962
PubMed ID:
24225324
Genetics
Abstract
Telomeres are terminal repetitive DNA sequences on chromosomes, and are considered to comprise almost exclusively hexameric TTAGGG repeats. We have evaluated telomere sequence content in human cells using whole-genome sequencing followed by telomere read extraction in a panel of mortal cell strains and immortal cell lines. We identified a wide range of telomere variant repeats in human cells, and found evidence that variant repeats are generated by mechanistically distinct processes during telomerase- and ALT-mediated telomere lengthening. Telomerase-mediated telomere extension resulted in biased repeat synthesis of variant repeats that differed from the canonical sequence at positions 1 and 3, but not at positions 2, 4, 5 or 6. This indicates that telomerase is most likely an error-prone reverse transcriptase that misincorporates nucleotides at specific positions on the telomerase RNA template. In contrast, cell lines that use the ALT pathway contained a large range of variant repeats that varied greatly between lines. This is consistent with variant repeats spreading from proximal telomeric regions throughout telomeres in a stochastic manner by recombination-mediated templating of DNA synthesis. The presence of unexpectedly large numbers of variant repeats in cells utilizing either telomere maintenance mechanism suggests a conserved role for variant sequences at human telomeres.
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Lee M. et al. Telomere extension by telomerase and ALT generates variant repeats by mechanistically distinct processes // Nucleic Acids Research. 2013. Vol. 42. No. 3. pp. 1733-1746.
GOST all authors (up to 50)
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Lee M., Hills M., Conomos D., Stutz M. D., Dagg R. A., Lau L., Reddel R., Pickett H. A. Telomere extension by telomerase and ALT generates variant repeats by mechanistically distinct processes // Nucleic Acids Research. 2013. Vol. 42. No. 3. pp. 1733-1746.
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TY - JOUR
DO - 10.1093/nar/gkt1117
UR - https://doi.org/10.1093%2Fnar%2Fgkt1117
TI - Telomere extension by telomerase and ALT generates variant repeats by mechanistically distinct processes
T2 - Nucleic Acids Research
AU - Lee, Michael
AU - Hills, Mark
AU - Conomos, Dimitri
AU - Stutz, Michael D
AU - Dagg, Rebecca A
AU - Lau, Loretta
AU - Reddel, R.R.
AU - Pickett, Hilda A.
PY - 2013
DA - 2013/11/12 00:00:00
PB - Oxford University Press
SP - 1733-1746
IS - 3
VL - 42
PMID - 24225324
SN - 0305-1048
SN - 1362-4962
ER -
Cite this
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@article{2013_Lee,
author = {Michael Lee and Mark Hills and Dimitri Conomos and Michael D Stutz and Rebecca A Dagg and Loretta Lau and R.R. Reddel and Hilda A. Pickett},
title = {Telomere extension by telomerase and ALT generates variant repeats by mechanistically distinct processes},
journal = {Nucleic Acids Research},
year = {2013},
volume = {42},
publisher = {Oxford University Press},
month = {nov},
url = {https://doi.org/10.1093%2Fnar%2Fgkt1117},
number = {3},
pages = {1733--1746},
doi = {10.1093/nar/gkt1117}
}
Cite this
MLA
Copy
Lee, Michael, et al. “Telomere extension by telomerase and ALT generates variant repeats by mechanistically distinct processes.” Nucleic Acids Research, vol. 42, no. 3, Nov. 2013, pp. 1733-1746. https://doi.org/10.1093%2Fnar%2Fgkt1117.