Bouziane M, Miao F, Bates S E, Somsouk L, Sang B C, Denissenko M, O'Connor T R
Department of Biology, Beckman Research Institute, City of Hope National Medical Center, 1450 East Duarte Road, Duarte, CA 91010, USA.
Mutat Res. 2000 Sep 15;461(1):15-29. doi: 10.1016/s0921-8777(00)00036-7.
The methylpurine-DNA glycosylase (MPG) gene coding for human 3-methyladenine (3-meAde)-DNA glycosylase functions in the first step of base excision repair (BER) to remove numerous damaged bases including 3-meGua, ethenoadenine, and hypoxanthine (Hx) in addition to 3-meAde. In this report, we identify the length of the minimal MPG promoter region, demonstrate the involvement of several transcription factors in expression of the MPG gene, and determine the point at which transcription initiates. We also demonstrate that control of MPG expression is linked to MPG activity. To initiate studies on how the MPG functions with the ensemble of BER genes to effect repair, we have investigated the cell cycle control of MPG and other BER genes in normal human cells. Steady-state mRNA levels of MPG, human Nth homologue (NTH), and uracil-DNA glycosylase (UDG), DNA glycosylases, and human AP site-specific endonuclease (APE), an endonuclease incising DNA at abasic sites, are cell cycle dependent. In contrast, expression levels of genes coding for human 8-oxoguanine-DNA glycosylase (OGG1) and TDG DNA glycosylases, and omicron 6-methylguanine-DNA methyltransferase (MGMT) gene, and the RPA4 subunit gene do not vary with cell cycle. These observed cell cycle dependent differences might reflect distinct roles of individual BER proteins in mutation avoidance.
编码人3-甲基腺嘌呤（3-meAde）-DNA糖基化酶的甲基嘌呤-DNA糖基化酶（MPG）基因在碱基切除修复（BER）的第一步发挥作用，除了3-meAde之外，还能去除许多受损碱基，包括3-meGua、乙烯腺嘌呤和次黄嘌呤（Hx）。在本报告中，我们确定了最小MPG启动子区域的长度，证明了几种转录因子参与MPG基因的表达，并确定了转录起始点。我们还证明了MPG表达的调控与MPG活性相关。为了开始研究MPG如何与BER基因整体协同作用以实现修复，我们研究了正常人细胞中MPG和其他BER基因的细胞周期调控。MPG、人Nth同源物（NTH）、尿嘧啶-DNA糖基化酶（UDG）、DNA糖基化酶以及人AP位点特异性内切酶（APE，一种在无碱基位点切割DNA的内切酶）的稳态mRNA水平是细胞周期依赖性的。相比之下，编码人8-氧代鸟嘌呤-DNA糖基化酶（OGG1）和TDG DNA糖基化酶的基因、奥密克戎6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）基因以及RPA4亚基基因的表达水平不随细胞周期变化。这些观察到的细胞周期依赖性差异可能反映了个体BER蛋白在避免突变中的不同作用。
