A centrosome-autonomous signal that involves centriole disengagement permits centrosome duplication in G2 phase after DNA damage.

Hdl Handle:
http://hdl.handle.net/10147/125266
Title:
A centrosome-autonomous signal that involves centriole disengagement permits centrosome duplication in G2 phase after DNA damage.
Authors:
Inanç, Burcu; Dodson, Helen; Morrison, Ciaran G
Affiliation:
Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland.
Citation:
A centrosome-autonomous signal that involves centriole disengagement permits centrosome duplication in G2 phase after DNA damage. 2010, 21 (22):3866-77 Mol. Biol. Cell
Journal:
Molecular biology of the cell
Issue Date:
15-Nov-2010
URI:
http://hdl.handle.net/10147/125266
DOI:
10.1091/mbc.E10-02-0124
PubMed ID:
20861312
Abstract:
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:
Article
Language:
en
MeSH:
Animals; Calcium-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
ISSN:
1939-4586

Full metadata record

DC FieldValue Language
dc.contributor.authorInanç, Burcuen
dc.contributor.authorDodson, Helenen
dc.contributor.authorMorrison, Ciaran Gen
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

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