Transcription Factors NF-YA Regulate the Induction of Human OGG1 Following DNA-alkylating Agent Methylmethane Sulfonate (MMS) Treatment

摘要: A human 8-oxoguanine-DNA glycosylase (hOGG1) is the main enzyme that repairs 8-oxoG, which a critical mutagenic lesion. There great deal of interest in up- or down-regulation OGG1 expression after DNA damage. In this study, we investigated effect DNA-alkylating agent, methylmethane sulfonate (MMS), on hOGG1 level and found MMS treatment resulted an increase functional HCT116 cells. region between –121 –61 promoter was to be crucial for induction by MMS. Site-directed mutations two inverted CCAAT motifs substantially abrogated as result treatment. addition, NF-YA protein (binding box) induced exposing cells Moreover, gel shift supershift analyses with nuclear extracts prepared from identified transcription factor interacting box. Mutations box either prevented binding abolished its activation Finally, study showed hOGG1-expressing exhibited increased repair activity resistance Overall, these results demonstrate can up-regulate through factor, NF-YA, gene correlates providing protection