Publication
DNA damage induces Chk1-dependent threonine-160 phosphorylation and activation of Cdk2
Publisher:
Springer Science and Business Media LLC
Date:
19-10-2009
DOI:
10.1038/ONC.2009.340
Abstract: Abnormal centrosome numbers arise in tumours and can cause multipolar mitoses and genome instability. Cdk2 controls normal centrosome duplication, but Chk1-dependent centrosome lification also occurs after DNA damage. We investigated the involvement of cyclin-dependent kinases (Cdks) in DNA damage-induced centrosome lification using cells lacking either Cdk2, or both Cdk1 and Cdk2 activity. Cdk2(-/-) DT40 cells showed robust centrosome lification after ionizing radiation (IR), whereas Cdk1-deficient Cdk2(-/-) cells showed no centrosome lification, 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 lification in Cdk1-deficient Cdk2(-/-) cells, but T160A mutation blocked this rescue. Our data suggest that Chk1 signalling causes centrosome lification after IR by upregulating Cdk2 activity through activating phosphorylation.