PARP-1 and gene regulation: Progress and puzzles

W. Lee Kraus, Michael O. Hottiger

Research output: Contribution to journalArticle

146 Scopus citations

Abstract

Poly(ADP-ribose) polymerase-1 (PARP-1), also referred to as ADP-ribosyltransferase Diphtheria toxin-like 1 (ARTD1), is an abundant nuclear protein that plays key roles in a variety of nuclear processes, including the regulation of transcription. PARP-1 possesses an intrinsic enzymatic activity that catalyzes the transfer of ADP-ribose (ADPR) units from nicotinamide adenine dinucleotide (NAD+) onto target gene regulatory proteins, thereby modulating their activities. Although great strides have been made in the past decade in deciphering the seemingly opposing and varied roles of PARP-1 in gene regulation, many puzzles remain. In this review, we discuss the current state of understanding in this area, especially how PARP-1 interfaces with various components of gene regulatory pathways (e.g., the basal transcription machinery, DNA-binding transcription factors, coregulators, chromatin remodeling, histone modifications, and DNA methylation). In addition, we discuss some gene-specific, cell type-specific, and cell state-specific effects of PARP-1 on gene regulation, which might contribute to its biological functions. Finally, we review some of the recent progress targeting PARPs using chemical inhibitors, some of which may alter PARP-1-dependent gene regulatory programs to promote therapeutic outcomes.

Original languageEnglish (US)
Pages (from-to)1109-1123
Number of pages15
JournalMolecular Aspects of Medicine
Volume34
Issue number6
DOIs
Publication statusPublished - Dec 2013

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Keywords

  • Activity
  • ADP-ribosylation
  • ARTD1
  • Chromatin
  • Gene expression
  • PARP-1
  • Poly(ADP-ribose)
  • Posttranslational modification
  • Regulation
  • Transcription

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Clinical Biochemistry
  • Medicine(all)

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