Phosphorylation of p65(RelA) on Ser(547) by ATM represses NF-κB-dependent transcription of specific genes after genotoxic stress.

The NF-κB pathway is involved in immune and inflammation responses, proliferation, differentiation and cell death or survival. It is activated by many external stimuli including genotoxic stress. DNA double-strand breaks activate NF-κB in an ATM-dependent manner.

Importance of PIKKs in NF-κB activation by genotoxic stress.

Alteration of the genome integrity leads to the activation of a vast network of cellular responses named "DNA damage response". Three kinases from the phosphoinositide 3-kinase-like protein kinase family regulate this network; ATM and DNA-PK both activated by DNA double-strand breaks and ATR activated by replication blocks. "DNA damage response" pathway coordinates cell cycle arrest, DNA repair, and the activation of transcription factors such as p53 and NF-κB.