GADD153, A GENE EXPRESSED IN RESPONSE TO DNA DAMAGE AND GROWTH ARREST

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The molecular response gene is also induced by growth arrest and with oxidative stress. It is likely that the gadd153 gene product plays a role in the cellular response to adversity, perhaps in controlling cell proliferation. Response to DNA damage: Induction of gadd153 gene expression following DNA damage is controlled primarily at the level of transcription. We have delineated sequences within the promoter region which are important for DNA damage-mediated activation of gadd153 transcription and have identified several features of gadd153 which make it unique among the DNA damage inducible genes: Activation of gadd153 transcription by DNA damage requires multiple elements within the promoter region and is protein kinase C sensitive. Induction by Growth Arrest: Using a gadd153 promoter-CAT reporter genewe have shown that medium depletion activates gadd153 transcription concurrent with growth arrest. Initial deletion analysis of the promoter region suggests that both positive and negative regulatory elements are important in controlling the expression of the gene with growth arrest.