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dc.contributor.authorInanc, B.
dc.contributor.authorDodson, H.
dc.contributor.authorMorrison, C. G.
dc.identifier.citationInanc, B. Dodson, H.; Morrison, C. G. (2010). A centrosome-autonomous signal that involves centriole disengagement permits centrosome duplication in g2 phase after dna damage. Molecular Biology of the Cell 21 (22), 3866-3877
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.publisherAmerican Society for Cell Biology (ASCB)
dc.relation.ispartofMolecular Biology of the Cell
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Ireland
dc.subjectpolo-like kinase-1
dc.subjecthamster ovary cells
dc.subjectdaughter centrioles
dc.subjectcancer progression
dc.subjectvertebrate cells
dc.titleA centrosome-autonomous signal that involves centriole disengagement permits centrosome duplication in g2 phase after dna damage

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Attribution-NonCommercial-NoDerivs 3.0 Ireland
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