Gadd45 proteins: key players of repair-mediated DNA demethylation

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.