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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2013
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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. |
format | Online Article Text |
id | pubmed-3639045 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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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