The ATF/CREB transcription factor-binding site in the polymerase β promoter mediates the positive effect of N-methyl-N′-nitro-N-nitrosoguanidine on transcription

Padmini S. Kedar, Steven G. Widen, Ella W. Englander, Albert J. Fornace, Samuel H. Wilson

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Abstract

DNA polymerase β(pol β) is a constitutively expressed DNA repair enzyme in vertebrate cells. Yet, it had been shown previously that the pol β mRNA level increases in Chinese hamster ovary (CHO) cells within 4 h after treatment with several monofunctional DNA damaging agents, notably, N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). Herein we report that a transfected pol β promoter fusion gene is activated by MNNG treatment of CHO cells; mRNA from the transfected gene is ≈ 10-fold higher in treated cells than in untreated cells 16 h after treatment. This activation is mediated through the decamicleotide palindromic element GTGACGTCAC at positions -49 to -40 in the "TATA-less" core promoter. This clement, which is similar to the ATF/CREB transcription factor-binding site in a number of mammalian genes, forms the center of a strong protein-binding site for CHO cell nuclear extract proteins. Mutated pol β promoter fusion genes lacking the element fail to bind protein at this site and fail to respond to MNNG treatment of cells.

Original languageEnglish (US)
Pages (from-to)3729-3733
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number9
DOIs
StatePublished - Jan 1 1991
Externally publishedYes

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