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A centrosome-autonomous signal that involves centriole disengagement permits centrosome duplication in g2 phase after dna damage
Inanc, B.; Dodson, H.; Morrison, C. G.
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.
Keyword(s): polo-like kinase-1; hamster ovary cells; cenp-f; daughter centrioles; ionizing-radiation; cancer progression; vertebrate cells; hela-cells; cho-cells; in-vivo
Publication Date:
2018
Type: Journal article
Peer-Reviewed: Unknown
Institution: NUI Galway
Publisher(s): American Society for Cell Biology (ASCB)
First Indexed: 2019-03-23 06:35:29 Last Updated: 2019-03-23 06:35:29