Parps and adp-ribosylation: Recent advances linking molecular functions to biological outcomes

Rebecca Gupte, Ziying Liu, W. Lee Kraus

Research output: Contribution to journalReview article

169 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)101-126
Number of pages26
JournalGenes and Development
Volume31
Issue number2
DOIs
StatePublished - Jan 15 2017

Keywords

  • DNA repair
  • Gene regulation
  • Mono(ADP-ribose) (MAR)
  • Poly (ADP-ribose) polymerase (PARP)
  • Poly(ADP-ribose) (PAR)
  • RNA biology

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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