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Five dysfunctional telomeres predict onset of senescence in human cells

Replicative senescence is accompanied by a telomere-specific DNA damage response (DDR). We found that DDR+ telomeres occur spontaneously in early-passage normal human cells and increase in number with increasing cumulative cell divisions. DDR+ telomeres at replicative senescence retain TRF2 and RAP1...

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Autores principales: Kaul, Zeenia, Cesare, Anthony J, Huschtscha, Lily I, Neumann, Axel A, Reddel, Roger R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: European Molecular Biology Organization 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246253/
https://www.ncbi.nlm.nih.gov/pubmed/22157895
http://dx.doi.org/10.1038/embor.2011.227
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author Kaul, Zeenia
Cesare, Anthony J
Huschtscha, Lily I
Neumann, Axel A
Reddel, Roger R
author_facet Kaul, Zeenia
Cesare, Anthony J
Huschtscha, Lily I
Neumann, Axel A
Reddel, Roger R
author_sort Kaul, Zeenia
collection PubMed
description Replicative senescence is accompanied by a telomere-specific DNA damage response (DDR). We found that DDR+ telomeres occur spontaneously in early-passage normal human cells and increase in number with increasing cumulative cell divisions. DDR+ telomeres at replicative senescence retain TRF2 and RAP1 proteins, are not associated with end-to-end fusions and mostly result from strand-independent, postreplicative dysfunction. On the basis of the calculated number of DDR+ telomeres in G1-phase cells just before senescence and after bypassing senescence by inactivation of wild-type p53 function, we conclude that the accrual of five telomeres in G1 that are DDR+ but nonfusogenic is associated with p53-dependent senescence.
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spelling pubmed-32462532012-01-03 Five dysfunctional telomeres predict onset of senescence in human cells Kaul, Zeenia Cesare, Anthony J Huschtscha, Lily I Neumann, Axel A Reddel, Roger R EMBO Rep Scientific Reports Replicative senescence is accompanied by a telomere-specific DNA damage response (DDR). We found that DDR+ telomeres occur spontaneously in early-passage normal human cells and increase in number with increasing cumulative cell divisions. DDR+ telomeres at replicative senescence retain TRF2 and RAP1 proteins, are not associated with end-to-end fusions and mostly result from strand-independent, postreplicative dysfunction. On the basis of the calculated number of DDR+ telomeres in G1-phase cells just before senescence and after bypassing senescence by inactivation of wild-type p53 function, we conclude that the accrual of five telomeres in G1 that are DDR+ but nonfusogenic is associated with p53-dependent senescence. European Molecular Biology Organization 2012-01 2011-12-09 /pmc/articles/PMC3246253/ /pubmed/22157895 http://dx.doi.org/10.1038/embor.2011.227 Text en Copyright © 2012, European Molecular Biology Organization https://creativecommons.org/licenses/by-nc-nd/3.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial No Derivative Works 3.0 Unported License, which permits distribution and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation or the creation of derivative works without specific permission.
spellingShingle Scientific Reports
Kaul, Zeenia
Cesare, Anthony J
Huschtscha, Lily I
Neumann, Axel A
Reddel, Roger R
Five dysfunctional telomeres predict onset of senescence in human cells
title Five dysfunctional telomeres predict onset of senescence in human cells
title_full Five dysfunctional telomeres predict onset of senescence in human cells
title_fullStr Five dysfunctional telomeres predict onset of senescence in human cells
title_full_unstemmed Five dysfunctional telomeres predict onset of senescence in human cells
title_short Five dysfunctional telomeres predict onset of senescence in human cells
title_sort five dysfunctional telomeres predict onset of senescence in human cells
topic Scientific Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246253/
https://www.ncbi.nlm.nih.gov/pubmed/22157895
http://dx.doi.org/10.1038/embor.2011.227
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