Fig. 2.

Sequence for the PQS in the coding strand of the VEGF gene that upon oxidation of G to OG provides a substrate for BER that unmasks the G-quadruplex for gene induction. (A) The sequence of the G-rich element in the VEGF promoter. The Gs marked in red are sites in which OG was synthetically incorporated to demonstrate the proposed pathway in part D [14]. (B) Data illustrating the presence of OG in the VEGF promoter increased luciferase expression by >2.5 fold in MEF cells, and knocking out OGG1 results in the signal remaining unchanged relative to the wild type (WT) plasmid. (C) Utility of APE1-specific siRNAs in glioblastoma cells provided a dose response impact on luciferase expression. The data in panels B and C demonstrate OGG1 and APE1, respectively, are required for gene induction when OG is present in the VEGF promoter PQS. These data were adapted from the original publication [14]. (D) Proposed pathway for oxidation of the PQS to yield OG and guide the BER process by unmasking the G-quadruplex for gene activation, thus illustrating an intertwining of DNA repair and transcriptional induction.