DNA Damage Signaling through Poly(ADP-Ribose).

Several lines of evidence reveal that poly(ADP-ribose)polymerase-1 (PARP-1) operates in a DNA damage signaling network. Poly(ADP-ribose) metabolism induced by DNA damage participates in DNA repair and contributes to downstream mechanisms leading to cell cycle arrest, cell survival, cell death, or cell transformation. An important element of these multiple actions is the recruitment of DNA damage checkpoint proteins coordinating DNA repair with downstream events. The focus of this overview is the mechanism by which poly(ADP-ribose)—attached to the automodified PARP-1—interact with DNA damage check-point proteins and how it may reprogram the functions of specific protein domains. Several proteins of the genome surveillance system, e.g., p53, p21, DNA-PK, NF-κB, XRCC1, and XPA are targets of such regulation. In all cass studied, a specific ‘polymer-binding' sequence motif of 20 to 26 amino acids is targeted by poly (ADP-ribose) and this motif overlaps with important functional domains responsible for protein-protein or protein-DNA interactions, nuclear import or export, enzymatic catalysis, or protein degradation. [ABSTRACT FROM AUTHOR]