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dc.contributor.authorBrown, J A L
dc.contributor.authorBourke, E
dc.contributor.authorLiptrot, C
dc.contributor.authorDockery, P
dc.contributor.authorMorrison, C G
dc.date.accessioned2018-09-20T16:01:46Z
dc.date.available2018-09-20T16:01:46Z
dc.date.issued2010-07-26
dc.identifier.citationBrown, J A L; Bourke, E; Liptrot, C; Dockery, P; Morrison, C G (2010). Mcph1/brit1 limits ionizing radiation-induced centrosome amplification. Oncogene 29 (40), 5537-5544
dc.identifier.issn0950-9232,1476-5594
dc.identifier.urihttp://hdl.handle.net/10379/10555
dc.description.abstractMicrocephalin (MCPH1/BRIT1) is a potential tumour suppressor that localizes to the centrosome, forms ionizing radiation-induced nuclear foci (IRIF) and is involved in the DNA damage checkpoints that ensure genome stability. Here, we report the impact of Mcph1 disruption in the hyper-recombinogenic DT40 cell line. Mcph1(-/-) cells were viable and proliferated at the same rate as wildtype controls. Mcph1-deficient cells had intact G2-to-M checkpoint responses after ionizing radiation (IR) treatment, but showed moderate radiosensitivity. Light and electron microscopy indicated normal centrosome structures in Mcph1 null cells, but IR induced massive amplification of centrosome numbers in the absence of Mcph1. Mcph1 null cells formed gamma-H2AX and Rad51 IRIF, but resolved them more slowly than wild-type cells. Mcph1 deficiency caused sustained Chk1 phosphorylation after IR, dysregulating Cdk2 activity. These findings show that Mcph1 controls centrosome numbers after DNA damage, which may indicate a novel tumour suppressive mechanism for microcephalin. Oncogene (2010) 29, 5537-5544; doi:10.1038/onc.2010.302; published online 26 July 2010
dc.publisherSpringer Nature
dc.relation.ispartofOncogene
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Ireland
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/3.0/ie/
dc.subjectmcph1/brit1
dc.subjectcentrosome
dc.subjectDNA damage response
dc.subjectcheckpoint
dc.subjectionizing radiation
dc.subjectDNA-damage response
dc.subjectstrand break repair
dc.subjecthomologous recombination
dc.subjectchromosome condensation
dc.subjectmitotic entry
dc.subjectmicrocephalin
dc.subjectprotein
dc.subjectcancer
dc.subjectactivation
dc.subjectcheckpoint
dc.titleMcph1/brit1 limits ionizing radiation-induced centrosome amplification
dc.typeArticle
dc.identifier.doi10.1038/onc.2010.302
dc.local.publishedsourcehttp://www.nature.com/onc/journal/v29/n40/pdf/onc2010302a.pdf
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