title: PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes.
abstract: The discovery of poly(ADP-ribose) >50 years ago opened a new field, leading the way for the discovery of the poly(ADP-ribose) polymerase (PARP) family of enzymes and the ADP-ribosylation reactions that they catalyze. Although the field was initially focused primarily on the biochemistry and molecular biology of PARP-1 in DNA damage detection and repair, the mechanistic and functional understanding of the role of PARPs in different biological processes has grown considerably of late. This has been accompanied by a shift of focus from enzymology to a search for substrates as well as the first attempts to determine the functional consequences of site-specific ADP-ribosylation on those substrates. Supporting these advances is a host of methodological approaches from chemical biology, proteomics, genomics, cell biology, and genetics that have propelled new discoveries in the field. New findings on the diverse roles of PARPs in chromatin regulation, transcription, RNA biology, and DNA repair have been complemented by recent advances that link ADP-ribosylation to stress responses, metabolism, viral infections, and cancer. These studies have begun to reveal the promising ways in which PARPs may be targeted therapeutically for the treatment of disease. In this review, we discuss these topics and relate them to the future directions of the field.
authors.affiliation: Laboratory of Signaling and Gene Regulation, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.|Division of Basic Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Gupte
authors.affiliation: Laboratory of Signaling and Gene Regulation, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.|Division of Basic Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Ziying
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Laboratory of Signaling and Gene Regulation, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.|Division of Basic Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: W Lee
authors.initials: WL
authors.lastname: Kraus
mesh_terms: D000818:Animals; D004260:DNA Repair / Q000235:genetics; D004789:Enzyme Activation; D054884:Host-Pathogen Interactions; D006801:Humans; D008967:Molecular Biology / Q000639:trends; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D011065:Poly(ADP-ribose) Polymerases; D009612:Nicotinamide-Nucleotide Adenylyltransferase
keywords: DNA repair; RNA biology; gene regulation; mono(ADP-ribose) (MAR); poly(ADP-ribose) (PAR); poly(ADP-ribose) polymerase (PARP)