GADD45

GADD45, or growth arrest and DNA damage-inducible 45, refers to a small family of genes that encode stress-responsive proteins involved in the cellular response to DNA damage and growth arrest. In humans the family comprises GADD45A, GADD45B, and GADD45G.

They are rapidly induced by DNA-damaging agents such as UV irradiation, ionizing radiation, and oxidative stress, as well as by oncogenic signaling. The GADD45 proteins regulate cell cycle progression and DNA repair. Mechanistically, they interact with PCNA to influence DNA repair and with upstream kinases to activate the p38 and JNK MAPK pathways, leading to cell cycle arrest or apoptosis depending on context.

GADD45A is a direct transcriptional target of p53 in some settings; other members are regulated by additional transcription factors and signaling pathways. They contribute to growth arrest at G2/M and can promote senescence. In cancer, GADD45 expression is frequently reduced, and restoration can inhibit tumor growth; however, roles can be context-dependent.

GADD45 proteins have been studied in cancer, aging, and response to therapy, and are used as markers of DNA damage response in research. Some studies suggest involvement in active DNA demethylation via DNA repair coupling, although mechanistic details remain debated.