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Rapid induction of Alternative Lengthening of Telomeres by depletion of the histone chaperone ASF1

The mechanism of activation of the Alternative Lengthening of Telomeres (ALT) pathway of mammalian chromosome end maintenance has remained an unresolved issue. We have discovered that co-depletion of the histone chaperones ASF1a and ASF1b in human cells induced all hallmarks of ALT in both primary a...

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Autores principales: O’Sullivan, Roderick J., Arnoult, Nausica, Lackner, Daniel H., Oganesian, Liana, Haggblom, Candy, Corpet, Armelle, Almouzni, Genevieve, Karlseder, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946341/
https://www.ncbi.nlm.nih.gov/pubmed/24413054
http://dx.doi.org/10.1038/nsmb.2754
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author O’Sullivan, Roderick J.
Arnoult, Nausica
Lackner, Daniel H.
Oganesian, Liana
Haggblom, Candy
Corpet, Armelle
Almouzni, Genevieve
Karlseder, Jan
author_facet O’Sullivan, Roderick J.
Arnoult, Nausica
Lackner, Daniel H.
Oganesian, Liana
Haggblom, Candy
Corpet, Armelle
Almouzni, Genevieve
Karlseder, Jan
author_sort O’Sullivan, Roderick J.
collection PubMed
description The mechanism of activation of the Alternative Lengthening of Telomeres (ALT) pathway of mammalian chromosome end maintenance has remained an unresolved issue. We have discovered that co-depletion of the histone chaperones ASF1a and ASF1b in human cells induced all hallmarks of ALT in both primary and cancer cells. These included the formation of ALT associated PML bodies (APBs), extra-chromosomal telomeric DNA species an elevated frequency of telomeric sister chromatid exchanges (t-SCE) events and inter-telomeric exchange of an integrated tag. The induction of ALT characteristics in this setting led to the simultaneous suppression of telomerase. We identified that ALT induction is positively regulated by RAD17 and BLM, while negatively regulated by EXO1 and DNA2. The induction of ALT phenotypes as a consequence of ASF1 depletion strongly support the hypothesis that ALT is a consequence of a histone management dysfunction.
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spelling pubmed-39463412014-08-01 Rapid induction of Alternative Lengthening of Telomeres by depletion of the histone chaperone ASF1 O’Sullivan, Roderick J. Arnoult, Nausica Lackner, Daniel H. Oganesian, Liana Haggblom, Candy Corpet, Armelle Almouzni, Genevieve Karlseder, Jan Nat Struct Mol Biol Article The mechanism of activation of the Alternative Lengthening of Telomeres (ALT) pathway of mammalian chromosome end maintenance has remained an unresolved issue. We have discovered that co-depletion of the histone chaperones ASF1a and ASF1b in human cells induced all hallmarks of ALT in both primary and cancer cells. These included the formation of ALT associated PML bodies (APBs), extra-chromosomal telomeric DNA species an elevated frequency of telomeric sister chromatid exchanges (t-SCE) events and inter-telomeric exchange of an integrated tag. The induction of ALT characteristics in this setting led to the simultaneous suppression of telomerase. We identified that ALT induction is positively regulated by RAD17 and BLM, while negatively regulated by EXO1 and DNA2. The induction of ALT phenotypes as a consequence of ASF1 depletion strongly support the hypothesis that ALT is a consequence of a histone management dysfunction. 2014-01-12 2014-02 /pmc/articles/PMC3946341/ /pubmed/24413054 http://dx.doi.org/10.1038/nsmb.2754 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
O’Sullivan, Roderick J.
Arnoult, Nausica
Lackner, Daniel H.
Oganesian, Liana
Haggblom, Candy
Corpet, Armelle
Almouzni, Genevieve
Karlseder, Jan
Rapid induction of Alternative Lengthening of Telomeres by depletion of the histone chaperone ASF1
title Rapid induction of Alternative Lengthening of Telomeres by depletion of the histone chaperone ASF1
title_full Rapid induction of Alternative Lengthening of Telomeres by depletion of the histone chaperone ASF1
title_fullStr Rapid induction of Alternative Lengthening of Telomeres by depletion of the histone chaperone ASF1
title_full_unstemmed Rapid induction of Alternative Lengthening of Telomeres by depletion of the histone chaperone ASF1
title_short Rapid induction of Alternative Lengthening of Telomeres by depletion of the histone chaperone ASF1
title_sort rapid induction of alternative lengthening of telomeres by depletion of the histone chaperone asf1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946341/
https://www.ncbi.nlm.nih.gov/pubmed/24413054
http://dx.doi.org/10.1038/nsmb.2754
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