DNA dynamics dictates p53 functional outcome

Abstract

AbstractThe tumor suppressor protein p53 is activated in response to cellular stress. An unresolved question in the field is how p53 is able to parse its myriad functions in a timely manner in accordance with the severity of the stress signal. Here we show across the genome that p53 target genes belonging to pathways acting early in the stress response have REs that are significantly more flexible than REs of genes involved in pathways that need to be more strictly regulated, or whose functional outcome occurs later in the response to stress. We validated these findings by several complementary experimental approaches, for six p53 REs belonging to pathways that operate at different times post p53 induction. Our results demonstrate that the flexibility of p53 REs contributes significantly to the temporal expression of p53 target genes and thereby to life versus death decisions in the p53 system.