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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...

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Detalles Bibliográficos
Autores principales: Li, Baomin, Reddy, Sita, Comai, Lucio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2011
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.
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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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AT comailucio depletionofku7080reducesthelevelsofextrachromosomaltelomericcirclesandinhibitsproliferationofaltcells