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

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.