This gene is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The protein encoded by this gene responds to environmental stresses by mediating activation of the p38/JNK pathway via MTK1/MEKK4 kinase. The DNA damage-induced transcription of this gene is mediated by both p53-dependent and -independent mechanisms.

Smith et al. (1994) found that GADD45 binds to PCNA, or proliferating cell nuclear antigen, a normal component of cyclin-dependent kinase complexes and a protein involved in DNA replication and repair. GADD45 stimulated DNA excision repair in vitro and inhibited entry of cells into S phase. These results established GADD45 as a link between the p53-dependent cell cycle checkpoint and DNA repair.