Gadd45 proteins: key players of repair-mediated DNA demethylation

Adv Exp Med Biol. 2013:793:35-50. doi: 10.1007/978-1-4614-8289-5_3.

Abstract

The three growth arrest and DNA damage 45 (Gadd45) family genes encode for stress-response proteins that are rapidly induced upon cellular stress or differentiation cues. They are well-characterized regulators of cell cycle, senescence, survival, and apoptosis. More recently, it has become clear that Gadd45 proteins promote active DNA demethylation thereby mediating gene activation. This epigenetic function of Gadd45 is important for differentiation and transcriptional regulation during development. Mechanistically, Gadd45 acts as an adapter for DNA repair factors at gene-specific loci to promote removal of 5-methylcytosine from DNA. Hence, Gadd45 is a nexus between DNA repair and epigenetic gene regulation.

Publication types

  • Review

MeSH terms

  • 5-Methylcytosine / metabolism
  • Animals
  • Antigens, Differentiation / genetics*
  • Antigens, Differentiation / metabolism
  • Apoptosis
  • Cell Cycle Checkpoints
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Differentiation
  • DNA / genetics
  • DNA Methylation
  • DNA Repair*
  • Epigenesis, Genetic*
  • Eukaryotic Cells / cytology
  • Eukaryotic Cells / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Signal Transduction

Substances

  • Antigens, Differentiation
  • Cell Cycle Proteins
  • GADD45A protein, human
  • GADD45B protein, human
  • GADD45G protein, human
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • 5-Methylcytosine
  • DNA