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The nucleolus stress response is coupled to an ATR-Chk1–mediated G2 arrest

We report experiments on the connection between nucleolar stress and cell cycle progression, using HeLa cells engineered with the fluorescent ubiquitinylation-based cell cycle indicator. Nucleolar stress elicited by brief exposure of cells to a low concentration of actinomycin D that selectively inh...

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Detalles Bibliográficos
Autores principales: Ma, Hanhui, Pederson, Thoru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639045/
https://www.ncbi.nlm.nih.gov/pubmed/23447702
http://dx.doi.org/10.1091/mbc.E12-12-0881
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author Ma, Hanhui
Pederson, Thoru
author_facet Ma, Hanhui
Pederson, Thoru
author_sort Ma, Hanhui
collection PubMed
description We report experiments on the connection between nucleolar stress and cell cycle progression, using HeLa cells engineered with the fluorescent ubiquitinylation-based cell cycle indicator. Nucleolar stress elicited by brief exposure of cells to a low concentration of actinomycin D that selectively inhibits rRNA synthesis had no effect on traverse of G1 or S, but stalled cells in very late interphase. Additional experiments revealed that a switch occurs during a specific temporal window during nucleolar stress and that the subsequent cell cycle arrest is not triggered simply by the stress-induced decline in the synthesis of rRNA or by a ribosome starvation phenomenon. Further experiments revealed that this nucleolus stress-induced cell cycle arrest involves the action of a G2 checkpoint mediated by the ataxia telangiectasia and Rad3-related protein (ATR)–checkpoint kinase 1 (Chk1) pathway. Based on analysis of the cell cycle stages at which this nucleolar stress effect is put into action, to become manifest later, our results demonstrate a feedforward mechanism that leads to G2 arrest and identify ATR and Chk1 as molecular agents of the requisite checkpoint.
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spelling pubmed-36390452013-07-16 The nucleolus stress response is coupled to an ATR-Chk1–mediated G2 arrest Ma, Hanhui Pederson, Thoru Mol Biol Cell Articles We report experiments on the connection between nucleolar stress and cell cycle progression, using HeLa cells engineered with the fluorescent ubiquitinylation-based cell cycle indicator. Nucleolar stress elicited by brief exposure of cells to a low concentration of actinomycin D that selectively inhibits rRNA synthesis had no effect on traverse of G1 or S, but stalled cells in very late interphase. Additional experiments revealed that a switch occurs during a specific temporal window during nucleolar stress and that the subsequent cell cycle arrest is not triggered simply by the stress-induced decline in the synthesis of rRNA or by a ribosome starvation phenomenon. Further experiments revealed that this nucleolus stress-induced cell cycle arrest involves the action of a G2 checkpoint mediated by the ataxia telangiectasia and Rad3-related protein (ATR)–checkpoint kinase 1 (Chk1) pathway. Based on analysis of the cell cycle stages at which this nucleolar stress effect is put into action, to become manifest later, our results demonstrate a feedforward mechanism that leads to G2 arrest and identify ATR and Chk1 as molecular agents of the requisite checkpoint. The American Society for Cell Biology 2013-05-01 /pmc/articles/PMC3639045/ /pubmed/23447702 http://dx.doi.org/10.1091/mbc.E12-12-0881 Text en © 2013 Ma and Pederson. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Ma, Hanhui
Pederson, Thoru
The nucleolus stress response is coupled to an ATR-Chk1–mediated G2 arrest
title The nucleolus stress response is coupled to an ATR-Chk1–mediated G2 arrest
title_full The nucleolus stress response is coupled to an ATR-Chk1–mediated G2 arrest
title_fullStr The nucleolus stress response is coupled to an ATR-Chk1–mediated G2 arrest
title_full_unstemmed The nucleolus stress response is coupled to an ATR-Chk1–mediated G2 arrest
title_short The nucleolus stress response is coupled to an ATR-Chk1–mediated G2 arrest
title_sort nucleolus stress response is coupled to an atr-chk1–mediated g2 arrest
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639045/
https://www.ncbi.nlm.nih.gov/pubmed/23447702
http://dx.doi.org/10.1091/mbc.E12-12-0881
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