PARP-1 and gene regulation: Progress and puzzles

W. Lee Kraus, Michael O. Hottiger

Research output: Contribution to journalArticle

142 Citations (Scopus)

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
StatePublished - Dec 2013

Fingerprint

Poly(ADP-ribose) Polymerases
Gene expression
Genes
Transcription
Regulator Genes
NAD
Histone Code
ADP Ribose Transferases
Adenosine Diphosphate Ribose
Gene Components
Diphtheria Toxin
Chromatin Assembly and Disassembly
DNA Methylation
Nuclear Proteins
Histones
Chromatin
Machinery
Poly (ADP-Ribose) Polymerase-1
Transcription Factors
DNA

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)

Cite this

PARP-1 and gene regulation : Progress and puzzles. / Kraus, W. Lee; Hottiger, Michael O.

In: Molecular Aspects of Medicine, Vol. 34, No. 6, 12.2013, p. 1109-1123.

Research output: Contribution to journalArticle

Kraus, W. Lee ; Hottiger, Michael O. / PARP-1 and gene regulation : Progress and puzzles. In: Molecular Aspects of Medicine. 2013 ; Vol. 34, No. 6. pp. 1109-1123.
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