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The absence of (TCAGGG)(n) repeats in some telomeres, combined with variable responses to NR2F2 depletion, suggest that this nuclear receptor plays an indirect role in the alternative lengthening of telomeres
The alternative lengthening of telomeres (ALT) facilitates telomere lengthening by a DNA strand invasion and copying mechanism. The nuclear receptors (NRs), NR2F2 and NR2C2, can bind to (TCAGGG)(n) variant repeats within telomeres and it has been proposed that this facilitates telomere interactions...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691514/ https://www.ncbi.nlm.nih.gov/pubmed/33244044 http://dx.doi.org/10.1038/s41598-020-77606-w |
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author | Alhendi, Ahmed S. N. Royle, Nicola J. |
author_facet | Alhendi, Ahmed S. N. Royle, Nicola J. |
author_sort | Alhendi, Ahmed S. N. |
collection | PubMed |
description | The alternative lengthening of telomeres (ALT) facilitates telomere lengthening by a DNA strand invasion and copying mechanism. The nuclear receptors (NRs), NR2F2 and NR2C2, can bind to (TCAGGG)(n) variant repeats within telomeres and it has been proposed that this facilitates telomere interactions in ALT+ cells. Here we show that the frequency of cells with detectable NR2F2 and NR2C2 nuclear foci varies considerably between ALT+ cell lines and does not correlate with the level of protein expression. In addition, four of five ALT+ cell lines lack (TCAGGG)(n) repeats in some telomeres, indicating that direct NR binding does not play a role in ALT at these telomeres. NR2F2-depletion altered the abundance of C-circles and APBs but the direction of the response was inconsistent between three ALT+ cell lines. Moreover, transcriptome analysis following NR2F2-depletion in the ALT+ cell lines revealed different very responses. For example, NR2F2-depletion down-regulated many genes in U2OS cells, consistent with the cell cycle arrest and changes to ALT markers, but these features were not shared by the other two ALT+ cell lines. Among 86 ALT-associated genes, only MND1 showed consistent down-regulation across three NR2F2-depleted ALT+ cell lines. Altogether our data suggest that NR2F2 does not play a direct role in ALT and we speculate about an alternative role for this NR in a DNA damage response at telomeres. |
format | Online Article Text |
id | pubmed-7691514 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-76915142020-11-27 The absence of (TCAGGG)(n) repeats in some telomeres, combined with variable responses to NR2F2 depletion, suggest that this nuclear receptor plays an indirect role in the alternative lengthening of telomeres Alhendi, Ahmed S. N. Royle, Nicola J. Sci Rep Article The alternative lengthening of telomeres (ALT) facilitates telomere lengthening by a DNA strand invasion and copying mechanism. The nuclear receptors (NRs), NR2F2 and NR2C2, can bind to (TCAGGG)(n) variant repeats within telomeres and it has been proposed that this facilitates telomere interactions in ALT+ cells. Here we show that the frequency of cells with detectable NR2F2 and NR2C2 nuclear foci varies considerably between ALT+ cell lines and does not correlate with the level of protein expression. In addition, four of five ALT+ cell lines lack (TCAGGG)(n) repeats in some telomeres, indicating that direct NR binding does not play a role in ALT at these telomeres. NR2F2-depletion altered the abundance of C-circles and APBs but the direction of the response was inconsistent between three ALT+ cell lines. Moreover, transcriptome analysis following NR2F2-depletion in the ALT+ cell lines revealed different very responses. For example, NR2F2-depletion down-regulated many genes in U2OS cells, consistent with the cell cycle arrest and changes to ALT markers, but these features were not shared by the other two ALT+ cell lines. Among 86 ALT-associated genes, only MND1 showed consistent down-regulation across three NR2F2-depleted ALT+ cell lines. Altogether our data suggest that NR2F2 does not play a direct role in ALT and we speculate about an alternative role for this NR in a DNA damage response at telomeres. Nature Publishing Group UK 2020-11-26 /pmc/articles/PMC7691514/ /pubmed/33244044 http://dx.doi.org/10.1038/s41598-020-77606-w Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Alhendi, Ahmed S. N. Royle, Nicola J. The absence of (TCAGGG)(n) repeats in some telomeres, combined with variable responses to NR2F2 depletion, suggest that this nuclear receptor plays an indirect role in the alternative lengthening of telomeres |
title | The absence of (TCAGGG)(n) repeats in some telomeres, combined with variable responses to NR2F2 depletion, suggest that this nuclear receptor plays an indirect role in the alternative lengthening of telomeres |
title_full | The absence of (TCAGGG)(n) repeats in some telomeres, combined with variable responses to NR2F2 depletion, suggest that this nuclear receptor plays an indirect role in the alternative lengthening of telomeres |
title_fullStr | The absence of (TCAGGG)(n) repeats in some telomeres, combined with variable responses to NR2F2 depletion, suggest that this nuclear receptor plays an indirect role in the alternative lengthening of telomeres |
title_full_unstemmed | The absence of (TCAGGG)(n) repeats in some telomeres, combined with variable responses to NR2F2 depletion, suggest that this nuclear receptor plays an indirect role in the alternative lengthening of telomeres |
title_short | The absence of (TCAGGG)(n) repeats in some telomeres, combined with variable responses to NR2F2 depletion, suggest that this nuclear receptor plays an indirect role in the alternative lengthening of telomeres |
title_sort | absence of (tcaggg)(n) repeats in some telomeres, combined with variable responses to nr2f2 depletion, suggest that this nuclear receptor plays an indirect role in the alternative lengthening of telomeres |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691514/ https://www.ncbi.nlm.nih.gov/pubmed/33244044 http://dx.doi.org/10.1038/s41598-020-77606-w |
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