PARP-nucleic acid interactions: Allosteric signaling, PARP inhibitor types, DNA bridges, and viral RNA surveillance

Abstract

PARP enzymes create ADP-ribose modifications to regulate multiple facets of human biology, and some prominent PARP family members are best known for the nucleic acid interactions that regulate their activities and functions. Recent structural studies have highlighted PARP interactions with nucleic acids, in particular for PARP enzymes that detect and respond to DNA strand break damage. These studies build on our understanding of how DNA break detection is linked to the catalysis of ADP-ribose modifications, provide insights into distinct modes of DNA interaction, and shed light on the mechanisms of PARP inhibitor action. PARP enzymes have several connections to RNA biology, including the detection of the genomes of RNA viruses, and recent structural work has highlighted how PARP13/ZAP specifically targets viral genomes enriched in CG dinucleotides.