A centrosome-autonomous signal that involves centriole disengagement permits centrosome duplication in G2 phase after DNA damage.
Affiliation
Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland.Issue Date
2010-11-15MeSH
AnimalsCalcium-Binding Proteins
Cell Cycle
Cell Cycle Proteins
Cell Line, Tumor
Centrioles
Centrosome
DNA Damage
G2 Phase
Humans
Immunoblotting
Luminescent Proteins
Microscopy, Fluorescence
Microtubule-Associated Proteins
Proliferating Cell Nuclear Antigen
S Phase
Signal Transduction
Time Factors
Metadata
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A centrosome-autonomous signal that involves centriole disengagement permits centrosome duplication in G2 phase after DNA damage. 2010, 21 (22):3866-77 Mol. Biol. CellJournal
Molecular biology of the cellDOI
10.1091/mbc.E10-02-0124PubMed ID
20861312Abstract
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.Item Type
ArticleLanguage
enISSN
1939-4586ae974a485f413a2113503eed53cd6c53
10.1091/mbc.E10-02-0124
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