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Variant repeats are interspersed throughout the telomeres and recruit nuclear receptors in ALT cells
Telomeres in cells that use the recombination-mediated alternative lengthening of telomeres (ALT) pathway elicit a DNA damage response that is partly independent of telomere length. We therefore investigated whether ALT telomeres contain structural abnormalities that contribute to ALT activity. Here...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518223/ https://www.ncbi.nlm.nih.gov/pubmed/23229897 http://dx.doi.org/10.1083/jcb.201207189 |
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author | Conomos, Dimitri Stutz, Michael D. Hills, Mark Neumann, Axel A. Bryan, Tracy M. Reddel, Roger R. Pickett, Hilda A. |
author_facet | Conomos, Dimitri Stutz, Michael D. Hills, Mark Neumann, Axel A. Bryan, Tracy M. Reddel, Roger R. Pickett, Hilda A. |
author_sort | Conomos, Dimitri |
collection | PubMed |
description | Telomeres in cells that use the recombination-mediated alternative lengthening of telomeres (ALT) pathway elicit a DNA damage response that is partly independent of telomere length. We therefore investigated whether ALT telomeres contain structural abnormalities that contribute to ALT activity. Here we used next generation sequencing to analyze the DNA content of ALT telomeres. We discovered that variant repeats were interspersed throughout the telomeres of ALT cells. We found that the C-type (TCAGGG) variant repeat predominated and created a high-affinity binding site for the nuclear receptors COUP-TF2 and TR4. Nuclear receptors were directly recruited to telomeres and ALT-associated characteristics were induced after incorporation of the C-type variant repeat by a mutant telomerase. We propose that the presence of variant repeats throughout ALT telomeres results from recombination-mediated telomere replication and spreading of variant repeats from the proximal regions of the telomeres and that the consequent binding of nuclear receptors alters the architecture of telomeres to facilitate further recombination. |
format | Online Article Text |
id | pubmed-3518223 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-35182232013-06-10 Variant repeats are interspersed throughout the telomeres and recruit nuclear receptors in ALT cells Conomos, Dimitri Stutz, Michael D. Hills, Mark Neumann, Axel A. Bryan, Tracy M. Reddel, Roger R. Pickett, Hilda A. J Cell Biol Research Articles Telomeres in cells that use the recombination-mediated alternative lengthening of telomeres (ALT) pathway elicit a DNA damage response that is partly independent of telomere length. We therefore investigated whether ALT telomeres contain structural abnormalities that contribute to ALT activity. Here we used next generation sequencing to analyze the DNA content of ALT telomeres. We discovered that variant repeats were interspersed throughout the telomeres of ALT cells. We found that the C-type (TCAGGG) variant repeat predominated and created a high-affinity binding site for the nuclear receptors COUP-TF2 and TR4. Nuclear receptors were directly recruited to telomeres and ALT-associated characteristics were induced after incorporation of the C-type variant repeat by a mutant telomerase. We propose that the presence of variant repeats throughout ALT telomeres results from recombination-mediated telomere replication and spreading of variant repeats from the proximal regions of the telomeres and that the consequent binding of nuclear receptors alters the architecture of telomeres to facilitate further recombination. The Rockefeller University Press 2012-12-10 /pmc/articles/PMC3518223/ /pubmed/23229897 http://dx.doi.org/10.1083/jcb.201207189 Text en © 2012 Conomos et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Conomos, Dimitri Stutz, Michael D. Hills, Mark Neumann, Axel A. Bryan, Tracy M. Reddel, Roger R. Pickett, Hilda A. Variant repeats are interspersed throughout the telomeres and recruit nuclear receptors in ALT cells |
title | Variant repeats are interspersed throughout the telomeres and recruit nuclear receptors in ALT cells |
title_full | Variant repeats are interspersed throughout the telomeres and recruit nuclear receptors in ALT cells |
title_fullStr | Variant repeats are interspersed throughout the telomeres and recruit nuclear receptors in ALT cells |
title_full_unstemmed | Variant repeats are interspersed throughout the telomeres and recruit nuclear receptors in ALT cells |
title_short | Variant repeats are interspersed throughout the telomeres and recruit nuclear receptors in ALT cells |
title_sort | variant repeats are interspersed throughout the telomeres and recruit nuclear receptors in alt cells |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518223/ https://www.ncbi.nlm.nih.gov/pubmed/23229897 http://dx.doi.org/10.1083/jcb.201207189 |
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