Peer-Reviewed Journal Details
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Inanc, B;Dodson, H;Morrison, CG
2010
November
Molecular Biology Of The Cell
A Centrosome-autonomous Signal That Involves Centriole Disengagement Permits Centrosome Duplication in G2 Phase after DNA Damage
Published
Altmetric: 2WOS: 34 ()
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POLO-LIKE KINASE-1 HAMSTER OVARY CELLS CENP-F DAUGHTER CENTRIOLES IONIZING-RADIATION CANCER PROGRESSION VERTEBRATE CELLS HELA-CELLS CHO-CELLS IN-VIVO
21
3866
3877
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.
1059-1524
10.1091/mbc.E10-02-0124
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