Promoter structure and cell cycle dependent expression of the human methylpurine-DNA glycosylase gene

The methylpurine-DNA glycosylase (MPG) gene coding for human 3-methyladenin e (3-meAde)-DNA glycosylase functions in the first step of base excision re pair (BER) to remove numerous damaged bases including 3-meGua, ethenoadenin e, and hypoxanthine (Hx) in addition to 3-meAde. In this report, we identif y the length of the minimal MPG promoter region, demonstrate the involvemen t of several transcription factors in expression of the MPG gene, and deter mine the point at which transcription initiates. We also demonstrate that c ontrol 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 h ave investigated the cell cycle control of MPG and other EER genes in norma l human cells. Steady-state mRNA levels of MPG, human Nth homologue (NTH), and uracil-DNA glycosylase (UDG), DNA glycosylases, and human AP site-speci fic endonuclease (APE), an endonuclease incising DNA at abasic sites, are c ell cycle dependent. In contrast, expression levels of genes coding for hum an 8-oxoguanine-DNA glycosylase (OGG1) and TDG DNA glycosylases, and O6-met hylguanine-DNA methyltransferase (MGMT) gene, and the RPA4 subunit gene do not vary with cell cycle. These observed cell cycle dependent differences m ight reflect distinct roles of individual EER proteins in mutation avoidanc e. (C) 2000 Elsevier Science B.V. All rights reserved.