The expanding universe of PARP1-mediated molecular and therapeutic mechanisms

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

ADP-ribosylation (ADPRylation) is a post-translational modification of proteins catalyzed by ADP-ribosyl transferase (ART) enzymes, including nuclear PARPs (e.g., PARP1 and PARP2). Historically, studies of ADPRylation and PARPs have focused on DNA damage responses in cancers, but more recent studies elucidate diverse roles in a broader array of biological processes. Here, we summarize the expanding array of molecular mechanisms underlying the biological functions of nuclear PARPs with a focus on PARP1, the founding member of the family. This includes roles in DNA repair, chromatin regulation, gene expression, ribosome biogenesis, and RNA biology. We also present new concepts in PARP1-dependent regulation, including PAR-dependent post-translational modifications, “ADPR spray,” and PAR-mediated biomolecular condensate formation. Moreover, we review advances in the therapeutic mechanisms of PARP inhibitors (PARPi) as well as the progress on the mechanisms of PARPi resistance. Collectively, the recent progress in the field has yielded new insights into the expanding universe of PARP1-mediated molecular and therapeutic mechanisms in a variety of biological processes.

Original languageEnglish (US)
JournalMolecular cell
DOIs
StateAccepted/In press - 2022

Keywords

  • ADP-ribosylation
  • biomolecular condensate
  • chromatin
  • DNA damage response
  • DNA replication
  • gene regulation
  • histone
  • PARP
  • PARP inhibitor
  • PARPi
  • poly(ADP-ribose) polymerase
  • post-translational modification
  • PTM
  • ribosome biogenesis
  • RNA biology
  • therapeutic resistance
  • therapeutics

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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