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F. He, X.-P. Yang, D.K. Srivastava, S.H. Wilson
DNA Polymerase ? Gene Expression: The Promoter Activator CREB-1 Is Upregulated in Chinese Hamster Ovary Cells by DNA Alkylating Agent-Induced Stress
The DNA alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) upregulates the level of the base excision DNA repair enzyme DNA polymerase ? (?-pol) in several mammalian cell types. Previous studies suggested that ?-pol expression is upregulated via a transcriptional mechanism that requires: the specific cAMP response element (CRE) in the ?-pol core promoter; a phosphorylated form of CREbinding protein-1 (CREB-1); and cellular protein kinase A activity. A large family of CRE-binding proteins, i.e., the ATF/CREB factors, has been identified in various cell types. This study further examines the role of CREbinding proteins in regulating ?-pol expression through study of Chinese hamster ovary (CHO) cells. In CHO cell nuclear extract, CREB-1 and ATF-1 are the predominant CRE-binding protein family members recognizing the CRE in the ?-pol core promoter. The concentration of CREB-1 increases strongly in CHO cells after exposure to MNNG. In contrast, the level of ATF-1 does not change after MNNG treatment. Recombinant expression of CREB-1 in CHO cells is sufficient to increase expression of the endogenous ?-pol gene, even in the absence of MNNG exposure. These results indicate that ?-pol gene expression in CHO cells can be upregulated by CREB-1 and that the activation of ?-pol gene expression in response to DNA alkylating agent exposure involves a strong increase in the level of CREB-1.
Biological Chemistry, Walter de Gruyter
Print ISSN: 1431-6730
Volume: 384, 01/2003
Pages: 19 - 23