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dc.contributor.authorBourke, E
dc.contributor.authorBrown, J A L
dc.contributor.authorTakeda, S
dc.contributor.authorHochegger, H
dc.contributor.authorMorrison, C G
dc.date.accessioned2018-09-20T16:01:25Z
dc.date.available2018-09-20T16:01:25Z
dc.date.issued2009-10-19
dc.identifier.citationBourke, E; Brown, J A L; Takeda, S; Hochegger, H; Morrison, C G (2009). Dna damage induces chk1-dependent threonine-160 phosphorylation and activation of cdk2. Oncogene 29 (4), 616-624
dc.identifier.issn0950-9232,1476-5594
dc.identifier.urihttp://hdl.handle.net/10379/10492
dc.description.abstractAbnormal centrosome numbers arise in tumours and can cause multipolar mitoses and genome instability. Cdk2 controls normal centrosome duplication, but Chk1-dependent centrosome amplification also occurs after DNA damage. We investigated the involvement of cyclin-dependent kinases (Cdks) in DNA damage-induced centrosome amplification using cells lacking either Cdk2, or both Cdk1 and Cdk2 activity. Cdk2(-/-) DT40 cells showed robust centrosome amplification after ionizing radiation (IR), whereas Cdk1-deficient Cdk2(-/-) cells showed no centrosome amplification, demonstrating that Cdk1 can substitute for Cdk2 in this pathway. Surprisingly, we found that Cdk2 activity was upregulated by IR in wild-type but not in Chk1(-/-) DT40 cells. Cdk2 upregulation also occurred in HeLa cells after IR treatment. Chk1-dependent Cdk2 induction was not accompanied by increased levels of Cdk1, Cdk2, cyclin A or cyclin E, but activating T160 phosphorylation of Cdk2 increased after IR. Moreover, Cdk2 overexpression restored IR-induced centrosome amplification in Cdk1-deficient Cdk2(-/-) cells, but T160A mutation blocked this rescue. Our data suggest that Chk1 signalling causes centrosome amplification after IR by upregulating Cdk2 activity through activating phosphorylation. Oncogene (2010) 29, 616-624; doi: 10.1038/onc.2009.340; published online 19 October 2009
dc.publisherSpringer Nature
dc.relation.ispartofOncogene
dc.subjectcentrosome
dc.subjectDNA damage response
dc.subjectchk1
dc.subjectcdk2
dc.subjectcdk1
dc.subjectinduced centrosome overduplication
dc.subjectcyclin-e overexpression
dc.subjectcell-cycle
dc.subjectchromosome instability
dc.subjecttumor-cells
dc.subjectamplification
dc.subjectphase
dc.subjectduplication
dc.subjectcheckpoint
dc.subjectcdc25a
dc.titleDna damage induces chk1-dependent threonine-160 phosphorylation and activation of cdk2
dc.typeArticle
dc.identifier.doi10.1038/onc.2009.340
dc.local.publishedsourcehttps://www.nature.com/articles/onc2009340.pdf
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