DNA damage leads to activation of TAp63, resulting in transcriptional induction of Puma and Noxa (which may be direct or indirect), with subsequent binding of PUMA and NOXA proteins to pro-survival BCL-2-family members (Bcl-2, Bcl-xL, Bcl-w, Mcl-1 or A1) and possibly also direct binding of PUMA to BAX/BAK. This causes activation of BAX and BAK, resulting in apoptotic cell death.