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Promyelocytic leukemia nuclear bodies behave as DNA damage sensors whose response to DNA double-strand breaks is regulated by NBS1 and the kinases ATM, Chk2, and ATR

The promyelocytic leukemia (PML) nuclear body (NB) is a dynamic subnuclear compartment that is implicated in tumor suppression, as well as in the transcription, replication, and repair of DNA. PML NB number can change during the cell cycle, increasing in S phase and in response to cellular stress, i...

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Autores principales: Dellaire, Graham, Ching, Reagan W., Ahmed, Kashif, Jalali, Farid, Tse, Kenneth C.K., Bristow, Robert G., Bazett-Jones, David P.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064496/
https://www.ncbi.nlm.nih.gov/pubmed/17030982
http://dx.doi.org/10.1083/jcb.200604009
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author Dellaire, Graham
Ching, Reagan W.
Ahmed, Kashif
Jalali, Farid
Tse, Kenneth C.K.
Bristow, Robert G.
Bazett-Jones, David P.
author_facet Dellaire, Graham
Ching, Reagan W.
Ahmed, Kashif
Jalali, Farid
Tse, Kenneth C.K.
Bristow, Robert G.
Bazett-Jones, David P.
author_sort Dellaire, Graham
collection PubMed
description The promyelocytic leukemia (PML) nuclear body (NB) is a dynamic subnuclear compartment that is implicated in tumor suppression, as well as in the transcription, replication, and repair of DNA. PML NB number can change during the cell cycle, increasing in S phase and in response to cellular stress, including DNA damage. Although topological changes in chromatin after DNA damage may affect the integrity of PML NBs, the molecular or structural basis for an increase in PML NB number has not been elucidated. We demonstrate that after DNA double-strand break induction, the increase in PML NB number is based on a biophysical process, as well as ongoing cell cycle progression and DNA repair. PML NBs increase in number by a supramolecular fission mechanism similar to that observed in S-phase cells, and which is delayed or inhibited by the loss of function of NBS1, ATM, Chk2, and ATR kinase. Therefore, an increase in PML NB number is an intrinsic element of the cellular response to DNA damage.
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spelling pubmed-20644962007-11-29 Promyelocytic leukemia nuclear bodies behave as DNA damage sensors whose response to DNA double-strand breaks is regulated by NBS1 and the kinases ATM, Chk2, and ATR Dellaire, Graham Ching, Reagan W. Ahmed, Kashif Jalali, Farid Tse, Kenneth C.K. Bristow, Robert G. Bazett-Jones, David P. J Cell Biol Research Articles The promyelocytic leukemia (PML) nuclear body (NB) is a dynamic subnuclear compartment that is implicated in tumor suppression, as well as in the transcription, replication, and repair of DNA. PML NB number can change during the cell cycle, increasing in S phase and in response to cellular stress, including DNA damage. Although topological changes in chromatin after DNA damage may affect the integrity of PML NBs, the molecular or structural basis for an increase in PML NB number has not been elucidated. We demonstrate that after DNA double-strand break induction, the increase in PML NB number is based on a biophysical process, as well as ongoing cell cycle progression and DNA repair. PML NBs increase in number by a supramolecular fission mechanism similar to that observed in S-phase cells, and which is delayed or inhibited by the loss of function of NBS1, ATM, Chk2, and ATR kinase. Therefore, an increase in PML NB number is an intrinsic element of the cellular response to DNA damage. The Rockefeller University Press 2006-10-09 /pmc/articles/PMC2064496/ /pubmed/17030982 http://dx.doi.org/10.1083/jcb.200604009 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Dellaire, Graham
Ching, Reagan W.
Ahmed, Kashif
Jalali, Farid
Tse, Kenneth C.K.
Bristow, Robert G.
Bazett-Jones, David P.
Promyelocytic leukemia nuclear bodies behave as DNA damage sensors whose response to DNA double-strand breaks is regulated by NBS1 and the kinases ATM, Chk2, and ATR
title Promyelocytic leukemia nuclear bodies behave as DNA damage sensors whose response to DNA double-strand breaks is regulated by NBS1 and the kinases ATM, Chk2, and ATR
title_full Promyelocytic leukemia nuclear bodies behave as DNA damage sensors whose response to DNA double-strand breaks is regulated by NBS1 and the kinases ATM, Chk2, and ATR
title_fullStr Promyelocytic leukemia nuclear bodies behave as DNA damage sensors whose response to DNA double-strand breaks is regulated by NBS1 and the kinases ATM, Chk2, and ATR
title_full_unstemmed Promyelocytic leukemia nuclear bodies behave as DNA damage sensors whose response to DNA double-strand breaks is regulated by NBS1 and the kinases ATM, Chk2, and ATR
title_short Promyelocytic leukemia nuclear bodies behave as DNA damage sensors whose response to DNA double-strand breaks is regulated by NBS1 and the kinases ATM, Chk2, and ATR
title_sort promyelocytic leukemia nuclear bodies behave as dna damage sensors whose response to dna double-strand breaks is regulated by nbs1 and the kinases atm, chk2, and atr
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064496/
https://www.ncbi.nlm.nih.gov/pubmed/17030982
http://dx.doi.org/10.1083/jcb.200604009
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