THE ATF CREB TRANSCRIPTION FACTOR-BINDING SITE IN THE POLYMERASE-BETA PROMOTER MEDIATES THE POSITIVE EFFECT OF N-METHYL-N'-NITRO-N-NITROSOGUANIDINE ON TRANSCRIPTION
THE ATF CREB TRANSCRIPTION FACTOR-BINDING SITE IN THE POLYMERASE-BETA PROMOTER MEDIATES THE POSITIVE EFFECT OF N-METHYL-N'-NITRO-N-NITROSOGUANIDINE ON TRANSCRIPTION
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DOI：
10.1073/pnas.88.9.3729
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发表时间：
1991-05-01
影响因子：
11.1
通讯作者：
WILSON, SH
中科院分区：
文献类型：
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作者：
KEDAR, PS;WIDEN, SG;WILSON, SH
DNA聚合酶-β（pol-beta）是脊椎动物细胞中组成型表达的DNA修复酶。 然而，先前已经表明，在用几种单功能DNA损伤剂，特别是N-甲基-N '-硝基-N-亚硝基胍（MNNG）处理后4小时内，中国仓鼠卵巢（CHO）细胞中的pol-beta mRNA水平增加。 在此，我们报告了转染的pol-beta-启动子融合基因通过MNNG处理CHO细胞而被激活;处理后16小时，来自转染基因的mRNA在处理的细胞中几乎等于在未处理的细胞中的10倍。 这种激活是通过“无TATA”核心启动子中-49至-40位的十核苷酸回文元件GTGACGTCAC介导的。 该元件与许多哺乳动物基因中的ATF/CREB转录因子结合位点相似，形成CHO细胞核提取物蛋白的强蛋白结合位点的中心。 缺乏该元件的突变的pol-β-启动子融合基因不能在该位点结合蛋白质，并且不能响应细胞的MNNG处理。
DNA polymerase-beta (pol-beta) is a constitutively expressed DNA repair enzyme in vertebrate cells. Yet, it had been shown previously that the pol-beta 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-beta-promoter fusion gene is activated by MNNG treatment of CHO cells; mRNA from the transfected gene is almost-equal-to 10-fold higher in treated cells than in untreated cells 16 h after treatment. This activation is mediated through the decanucleotide palindromic element GTGACGTCAC at positions -49 to -40 in the "TATA-less" core promoter. This element, 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-beta-promoter fusion genes lacking the element fail to bind protein at this site and fail to respond to MNNG treatment of cells.