Figure 6. Schematic model of the two‐phase NF‐κB activation after DNA damage.

DNA damage triggers two phases of NF‐κB activation and two distinct transcriptomes: anti‐apoptotic and inflammatory. NF‐κB is rapidly activated through the known genotoxic stress‐induced IKK cascade, resulting in proteasome‐dependent IκBα degradation and expression of first‐phase target genes, including IκBα. NF‐κB activation in senescence is caused by a loss of IκBα expression through a largely IKK‐ and proteasome‐independent mechanism and drives SASP expression.