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The Growth Arrest and DNA Damage or gadd45 genes, including GADD45A (originally termed gadd45) GADD45B (originally termed MyD118), and GADD45G (originally termed CR6), are implicated as stress sensors that modulate the response of mammalian cells to genotoxic/physiological stress, and modulate tumor formation. Gadd45 proteins interact with other proteins implicated in stress responses, including PCNA, p21, Cdc2/CyclinB1, MEKK4, and p38 kinase.[1][2]

GADD45 proteins regulate differentiation at the two cell stage of embryogenesis, a key stage of zygotic genome activation.[3] GADD45 likely acts by promoting TET-mediated DNA demethylation leading to the induction of expression of genes necessary for zygote activation.


  • Gadd45a was discovered and characterized in the laboratory of Dr. Albert J. Fornace Jr. in 1988.[4]
  • Gadd45b (MyD118) was discovered and characterized in the laboratories of Drs. Dan A. Liebermann and Barbara Hoffman in 1991.[5]
  • Gadd45g (CR6) was discovered and characterized in the laboratories of Drs. Kenneth Smith, Dan A. Liebermann, and Barbara Hoffman in 1993 and 1999.[6][7]

See also[edit]


  1. ^ Fornace, A.J.; Jackman, J.; Hollander, M.C.; Hoffman-Liebermann, B.; Liebermann, D.A. (1992). "Genotoxic-stress-response genes and growth-arrest genes: gadd, MyD, and other genes induced by treatments eliciting growth arrest". Annals of the New York Academy of Sciences. 663: 139–53. doi:10.1111/j.1749-6632.1992.tb38657.x. PMID 1482047.
  2. ^ Liebermann, D.A.; Hoffman, B. (2002). "Myeloid differentiation (MyD)/growth arrest DNA damage (GADD) genes in tumor suppression, immunity and inflammation". Leukemia. 16 (4): 527–41. doi:10.1038/sj.leu.2402477. PMID 11960329.
  3. ^ Schüle KM, Leichsenring M, Andreani T, Vastolo V, Mallick M, Musheev MU, Karaulanov E, Niehrs C. GADD45 promotes locus-specific DNA demethylation and 2C cycling in embryonic stem cells. Genes Dev. 2019 Jul 1;33(13-14):782-798. doi: 10.1101/gad.325696.119. Epub 2019 Jun 6. PMID: 31171699
  4. ^ Fornace, A.J.; Alamo, I.; Hollander, M.C. (1988). "DNA damage-inducible transcripts in mammalian cells". Proceedings of the National Academy of Sciences. 85 (23): 8800–4. doi:10.1073/pnas.85.23.8800. PMC 282594. PMID 3194391.
  5. ^ Abdollahi, A.; Lord, K.A.; Hoffman-Liebermann, B.; Liebermann, D.A. (1991). "Sequence and expression of a cDNA encoding MyD118: a novel myeloid differentiation primary response gene induced by multiple cytokines". Oncogene. 6 (1): 165–7. PMID 1899477.
  6. ^ Zhang, W.; Bae, I.; Krishnaraju, K.; Azam, Naiyer; et al. (1999). "CR6: A third member in the MyD118 and Gadd45 gene family which functions in negative growth control". Oncogene. 18 (35): 4899–907. doi:10.1038/sj.onc.1202885. PMID 10490824.
  7. ^ Beadling, C.; Johnson, K.W.; Smith, K.A. (1993). "Isolation of interleukin 2-induced immediate-early genes". Proceedings of the National Academy of Sciences. 90 (7): 2719–23. doi:10.1073/pnas.90.7.2719. PMC 46167. PMID 7681987.

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