RT Journal Article
SR Electronic
T1 Cdk activity drives senescence from G2 phase
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 041723
DO 10.1101/041723
A1 Erik Müllers
A1 Helena Silva Cascales
A1 Libor Macurek
A1 Arne Lindqvist
YR 2016
UL http://biorxiv.org/content/early/2016/02/29/041723.abstract
AB 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 is retained after DNA damage until terminal cell cycle exit. The low level of Cdk activity not only allows cell cycle progression, but also forces cell cycle exit at a decision point in G2 phase. We find that Cdk activity stimulates p21 production, leading to 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 drives senescence in the presence of DNA damage, ensuring a robust response when most needed.