Loss of p21 CDKN1A impairs entry to quiescence and activates a DNA damage response in normal fibroblasts induced to quiescence.

The cell cycle inhibitor p21(CDKN1A) induces cell cycle arrest under different conditions, including senescence and terminal differentiation. Still debated is its involvement in the reversible transition from proliferation to a non-dividing quiescent state (G(0)), in which a significant role has been attributed to cell cycle inhibitor p27(CDKN1B). Here we provide evidence showing that high p21 protein levels are necessary to enter and maintain the quiescence state following contact inhibition and growth factor withdrawal.