PARP-1 mechanism for coupling DNA damage detection to poly(ADP-ribose) synthesis

► PARP-1 zinc finger domains recognize exposed nucleotide bases as a DNA damage signal. ► The modular domain architecture of PARP-1 collapses onto DNA damage as a monomer. ► Interdomain communication is critical to PARP-1 activation in response to DNA damage. ► A destabilized PARP-1 catalytic domain has increased poly(ADP-ribosyl)ation activity.