dc.contributor.author | Bourke, E | |
dc.contributor.author | Brown, J A L | |
dc.contributor.author | Takeda, S | |
dc.contributor.author | Hochegger, H | |
dc.contributor.author | Morrison, C G | |
dc.date.accessioned | 2018-09-20T16:01:25Z | |
dc.date.available | 2018-09-20T16:01:25Z | |
dc.date.issued | 2009-10-19 | |
dc.identifier.citation | Bourke, 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.issn | 0950-9232,1476-5594 | |
dc.identifier.uri | http://hdl.handle.net/10379/10492 | |
dc.description.abstract | Abnormal 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.publisher | Springer Nature | |
dc.relation.ispartof | Oncogene | |
dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Ireland | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/3.0/ie/ | |
dc.subject | centrosome | |
dc.subject | DNA damage response | |
dc.subject | chk1 | |
dc.subject | cdk2 | |
dc.subject | cdk1 | |
dc.subject | induced centrosome overduplication | |
dc.subject | cyclin-e overexpression | |
dc.subject | cell-cycle | |
dc.subject | chromosome instability | |
dc.subject | tumor-cells | |
dc.subject | amplification | |
dc.subject | phase | |
dc.subject | duplication | |
dc.subject | checkpoint | |
dc.subject | cdc25a | |
dc.title | Dna damage induces chk1-dependent threonine-160 phosphorylation and activation of cdk2 | |
dc.type | Article | |
dc.identifier.doi | 10.1038/onc.2009.340 | |
dc.local.publishedsource | https://www.nature.com/articles/onc2009340.pdf | |
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