Open AccessResidual Cdk1/2 activity after DNA damage promotes senescence
Author(s) -
Müllers Erik,
Silva Cascales Helena,
Burdova Kamila,
Macurek Libor,
Lindqvist Arne
Publication year - 2017
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12588
Subject(s) - biology , senescence , microbiology and biotechnology , cell cycle , mitosis , restriction point , cyclin dependent kinase , dna damage , cdk inhibitor , cyclin dependent kinase 1 , cell cycle checkpoint , cell cycle protein , cell , dna , genetics
Summary 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 / C C dh1 ‐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.