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Aging Cell. 2017 Jun;16(3):575-584. doi: 10.1111/acel.12588. Epub 2017 Mar 26.

Residual Cdk1/2 activity after DNA damage promotes senescence.

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Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Laboratory of Cancer Cell Biology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.


In response to DNA damage, a cell can be forced to permanently exit the cell cycle and become senescent. Senescence provides an early barrier against tumor development by preventing proliferation of cells with damaged DNA. By studying single cells, we show that Cdk activity persists after DNA damage until terminal cell cycle exit. This low level of Cdk activity not only allows cell cycle progression, but also promotes cell cycle exit at a decision point in G2 phase. We find that residual Cdk1/2 activity is required for efficient p21 production, allowing for nuclear sequestration of Cyclin B1, subsequent APC/CCdh1 -dependent degradation of mitotic inducers and induction of senescence. We suggest that the same activity that triggers mitosis in an unperturbed cell cycle enforces senescence in the presence of DNA damage, ensuring a robust response when most needed.


Cdk1; Cdk2; DNA damage response; G2 phase; cell cycle; checkpoint recovery; p21; senescence

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