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dc.contributor.authorInanç, Burcu
dc.contributor.authorDodson, Helen
dc.contributor.authorMorrison, Ciaran G
dc.date.accessioned2011-03-21T16:21:57Z
dc.date.available2011-03-21T16:21:57Z
dc.date.issued2010-11-15
dc.identifier.citationA centrosome-autonomous signal that involves centriole disengagement permits centrosome duplication in G2 phase after DNA damage. 2010, 21 (22):3866-77 Mol. Biol. Cellen
dc.identifier.issn1939-4586
dc.identifier.pmid20861312
dc.identifier.doi10.1091/mbc.E10-02-0124
dc.identifier.urihttp://hdl.handle.net/10147/125266
dc.description.abstractDNA 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.
dc.language.isoenen
dc.subject.meshAnimals
dc.subject.meshCalcium-Binding Proteins
dc.subject.meshCell Cycle
dc.subject.meshCell Cycle Proteins
dc.subject.meshCell Line, Tumor
dc.subject.meshCentrioles
dc.subject.meshCentrosome
dc.subject.meshDNA Damage
dc.subject.meshG2 Phase
dc.subject.meshHumans
dc.subject.meshImmunoblotting
dc.subject.meshLuminescent Proteins
dc.subject.meshMicroscopy, Fluorescence
dc.subject.meshMicrotubule-Associated Proteins
dc.subject.meshProliferating Cell Nuclear Antigen
dc.subject.meshS Phase
dc.subject.meshSignal Transduction
dc.subject.meshTime Factors
dc.titleA centrosome-autonomous signal that involves centriole disengagement permits centrosome duplication in G2 phase after DNA damage.en
dc.typeArticleen
dc.contributor.departmentCentre for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland.en
dc.identifier.journalMolecular biology of the cellen
html.description.abstractDNA 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.


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