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Depletion of Ku70/80 reduces the levels of extrachromosomal telomeric circles and inhibits proliferation of ALT cells
In normal cells, telomeres shorten each time a cell divides ultimately resulting in cell senescence. t In contrast, cancer cells counteract the loss of telomeric DNA either by inducing the expression of telomerase or by activating the Alternative Lengthening of Telomeres (ALT) pathway. ALT cells are...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3117455/ https://www.ncbi.nlm.nih.gov/pubmed/21512205 |
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author | Li, Baomin Reddy, Sita Comai, Lucio |
author_facet | Li, Baomin Reddy, Sita Comai, Lucio |
author_sort | Li, Baomin |
collection | PubMed |
description | In normal cells, telomeres shorten each time a cell divides ultimately resulting in cell senescence. t In contrast, cancer cells counteract the loss of telomeric DNA either by inducing the expression of telomerase or by activating the Alternative Lengthening of Telomeres (ALT) pathway. ALT cells are characterized by heterogeneous telomeres and the presence of extrachromosomal circular double-stranded DNA molecules containing telomeric repeat sequences. These telomeric circles (t-circles) are thought to be generated through a recombination process and utilized as templates for telomere elongation by rolling-circle-replication, although their precise mechanism of formation and role in telomere maintenance and cell proliferation is largely unknown. Here we show that shRNA-mediated knockdown of the Ku70/80 heterodimer, a factor with functions at both pathological and natural DNA ends, inhibits ALT cell growth and results in a significant decrease in the levels of t-circles without affecting overall telomere length. These findings demonstrate that non homology-based processes contribute to the maintenance of t-circles and proliferation of ALT cells. |
format | Online Article Text |
id | pubmed-3117455 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-31174552011-06-20 Depletion of Ku70/80 reduces the levels of extrachromosomal telomeric circles and inhibits proliferation of ALT cells Li, Baomin Reddy, Sita Comai, Lucio Aging (Albany NY) Research Paper In normal cells, telomeres shorten each time a cell divides ultimately resulting in cell senescence. t In contrast, cancer cells counteract the loss of telomeric DNA either by inducing the expression of telomerase or by activating the Alternative Lengthening of Telomeres (ALT) pathway. ALT cells are characterized by heterogeneous telomeres and the presence of extrachromosomal circular double-stranded DNA molecules containing telomeric repeat sequences. These telomeric circles (t-circles) are thought to be generated through a recombination process and utilized as templates for telomere elongation by rolling-circle-replication, although their precise mechanism of formation and role in telomere maintenance and cell proliferation is largely unknown. Here we show that shRNA-mediated knockdown of the Ku70/80 heterodimer, a factor with functions at both pathological and natural DNA ends, inhibits ALT cell growth and results in a significant decrease in the levels of t-circles without affecting overall telomere length. These findings demonstrate that non homology-based processes contribute to the maintenance of t-circles and proliferation of ALT cells. Impact Journals LLC 2011-04-15 /pmc/articles/PMC3117455/ /pubmed/21512205 Text en Copyright: © 2011 Li et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
spellingShingle | Research Paper Li, Baomin Reddy, Sita Comai, Lucio Depletion of Ku70/80 reduces the levels of extrachromosomal telomeric circles and inhibits proliferation of ALT cells |
title | Depletion of Ku70/80 reduces the levels of extrachromosomal telomeric circles and inhibits proliferation of ALT cells |
title_full | Depletion of Ku70/80 reduces the levels of extrachromosomal telomeric circles and inhibits proliferation of ALT cells |
title_fullStr | Depletion of Ku70/80 reduces the levels of extrachromosomal telomeric circles and inhibits proliferation of ALT cells |
title_full_unstemmed | Depletion of Ku70/80 reduces the levels of extrachromosomal telomeric circles and inhibits proliferation of ALT cells |
title_short | Depletion of Ku70/80 reduces the levels of extrachromosomal telomeric circles and inhibits proliferation of ALT cells |
title_sort | depletion of ku70/80 reduces the levels of extrachromosomal telomeric circles and inhibits proliferation of alt cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3117455/ https://www.ncbi.nlm.nih.gov/pubmed/21512205 |
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