Poly(ADP-ribose): A Dynamic Trigger for Biomolecular Condensate Formation

Research output: Contribution to journalReview article

Abstract

Poly(ADP-ribose) (PAR) is a nucleic acid-like protein modification that can seed the formation of microscopically visible cellular compartments that lack enveloping membranes, recently termed biomolecular condensates. These PAR-mediated condensates are linked to cancer, viral infection, and neurodegeneration. Recent data have shown the therapeutic potential of modulating PAR conjugation (PARylation): PAR polymerase (PARP) inhibitors can modulate the formation and dynamics of these condensates as well as the trafficking of their components – many of which are key disease factors. However, the way in which PARylation facilitates these functions remains unclear, partly because of our lack of understanding of the fundamental parameters of intracellular PARylation, including the sites that are conjugated, PAR chain length and structure, and the physicochemical properties of the conjugates. This review first introduces the role of PARylation in regulating biomolecular condensates, followed by discussion of current knowledge gaps, potential solutions, and therapeutic applications.

Original languageEnglish (US)
Pages (from-to)370-383
Number of pages14
JournalTrends in Cell Biology
Volume30
Issue number5
DOIs
StatePublished - May 2020

Keywords

  • ADP-ribosylation
  • biomolecular condensate
  • liquid–liquid phase separation
  • poly(ADP-ribose)
  • poly(ADP-ribose) polymerase
  • poly(ADP-ribose) polymerase inhibitor

ASJC Scopus subject areas

  • Cell Biology

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