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A Centrosome-autonomous Signal That Involves Centriole Disengagement Permits Centrosome Duplication in G2 Phase after DNA Damage
DNA damage can induce centrosome overduplication in a manner that requires G2-to-M checkpoint function, suggesting that genotoxic stress can decouple the centrosome and chromosome cycles. How this happens is unclear. Using live-cell imaging of cells that express fluorescently tagged NEDD1/GCP-WD and...
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
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The American Society for Cell Biology
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2982117/ https://www.ncbi.nlm.nih.gov/pubmed/20861312 http://dx.doi.org/10.1091/mbc.E10-02-0124 |
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author | Inanç, Burcu Dodson, Helen Morrison, Ciaran G. |
author_facet | Inanç, Burcu Dodson, Helen Morrison, Ciaran G. |
author_sort | Inanç, Burcu |
collection | PubMed |
description | DNA damage can induce centrosome overduplication in a manner that requires G2-to-M checkpoint function, suggesting that genotoxic stress can decouple the centrosome and chromosome cycles. How this happens is unclear. Using live-cell imaging of cells that express fluorescently tagged NEDD1/GCP-WD and proliferating cell nuclear antigen, we found that ionizing radiation (IR)-induced centrosome amplification can occur outside S phase. Analysis of synchronized populations showed that significantly more centrosome amplification occurred after irradiation of G2-enriched populations compared with G1-enriched or asynchronous cells, consistent with G2 phase centrosome amplification. Irradiated and control populations of G2 cells were then fused to test whether centrosome overduplication is allowed through a diffusible stimulatory signal, or the loss of a duplication-inhibiting signal. Irradiated G2/irradiated G2 cell fusions showed significantly higher centrosome amplification levels than irradiated G2/unirradiated G2 fusions. Chicken–human cell fusions demonstrated that centrosome amplification was limited to the irradiated partner. Our finding that only the irradiated centrosome can duplicate supports a model where a centrosome-autonomous inhibitory signal is lost upon irradiation of G2 cells. We observed centriole disengagement after irradiation. Although overexpression of dominant-negative securin did not affect IR-induced centrosome amplification, Plk1 inhibition reduced radiation-induced amplification. Together, our data support centriole disengagement as a licensing signal for DNA damage-induced centrosome amplification. |
format | Text |
id | pubmed-2982117 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-29821172011-01-30 A Centrosome-autonomous Signal That Involves Centriole Disengagement Permits Centrosome Duplication in G2 Phase after DNA Damage Inanç, Burcu Dodson, Helen Morrison, Ciaran G. Mol Biol Cell Articles DNA damage can induce centrosome overduplication in a manner that requires G2-to-M checkpoint function, suggesting that genotoxic stress can decouple the centrosome and chromosome cycles. How this happens is unclear. Using live-cell imaging of cells that express fluorescently tagged NEDD1/GCP-WD and proliferating cell nuclear antigen, we found that ionizing radiation (IR)-induced centrosome amplification can occur outside S phase. Analysis of synchronized populations showed that significantly more centrosome amplification occurred after irradiation of G2-enriched populations compared with G1-enriched or asynchronous cells, consistent with G2 phase centrosome amplification. Irradiated and control populations of G2 cells were then fused to test whether centrosome overduplication is allowed through a diffusible stimulatory signal, or the loss of a duplication-inhibiting signal. Irradiated G2/irradiated G2 cell fusions showed significantly higher centrosome amplification levels than irradiated G2/unirradiated G2 fusions. Chicken–human cell fusions demonstrated that centrosome amplification was limited to the irradiated partner. Our finding that only the irradiated centrosome can duplicate supports a model where a centrosome-autonomous inhibitory signal is lost upon irradiation of G2 cells. We observed centriole disengagement after irradiation. Although overexpression of dominant-negative securin did not affect IR-induced centrosome amplification, Plk1 inhibition reduced radiation-induced amplification. Together, our data support centriole disengagement as a licensing signal for DNA damage-induced centrosome amplification. The American Society for Cell Biology 2010-11-15 /pmc/articles/PMC2982117/ /pubmed/20861312 http://dx.doi.org/10.1091/mbc.E10-02-0124 Text en © 2010 by The American Society for Cell Biology 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). |
spellingShingle | Articles Inanç, Burcu Dodson, Helen Morrison, Ciaran G. A Centrosome-autonomous Signal That Involves Centriole Disengagement Permits Centrosome Duplication in G2 Phase after DNA Damage |
title | A Centrosome-autonomous Signal That Involves Centriole Disengagement Permits Centrosome Duplication in G2 Phase after DNA Damage |
title_full | A Centrosome-autonomous Signal That Involves Centriole Disengagement Permits Centrosome Duplication in G2 Phase after DNA Damage |
title_fullStr | A Centrosome-autonomous Signal That Involves Centriole Disengagement Permits Centrosome Duplication in G2 Phase after DNA Damage |
title_full_unstemmed | A Centrosome-autonomous Signal That Involves Centriole Disengagement Permits Centrosome Duplication in G2 Phase after DNA Damage |
title_short | A Centrosome-autonomous Signal That Involves Centriole Disengagement Permits Centrosome Duplication in G2 Phase after DNA Damage |
title_sort | centrosome-autonomous signal that involves centriole disengagement permits centrosome duplication in g2 phase after dna damage |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2982117/ https://www.ncbi.nlm.nih.gov/pubmed/20861312 http://dx.doi.org/10.1091/mbc.E10-02-0124 |
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