The persistence of memory

Live imaging reveals that whether or not a daughter cell proliferates is influenced by two molecular factors inherited from its mother, providing insight into how the behaviour of a newly born cell can be predetermined. See Letter p.404 Signaling memories maximize healthy cell growth When a proliferating population of cells complete mitosis, some newly born daughter cells immediately enter the next cell cycle whereas other cells exit to a quiescent state. Here, Tobias Meyer and colleagues show that cells make this cell-cycle entry or exit decision on the basis of competing memories of variable mitogen and stress signals. They find that mother cells transmit mitogen-induced cyclin D1 mRNA and DNA-damage-induced p53 protein to newly born daughter cells, and the daughter cells control the decision between proliferation and quiescence by inducing variable expression of cyclin D1 and the p53-regulated CDK inhibitor p21. These molecules compete by a stoichiometric inhibition mechanism to determine cell-cycle commitment. The authors propose a model for cell-cycle control that maximizes the health of growing cell populations by preferentially selecting cells with a history of low DNA damage for more frequent proliferation.