8-Oxo-7,8-dihydroguanine in the Context of a Gene Promoter G-Quadruplex Is an On-Off Switch for Transcription.

ABSTRACT: Interplay between DNA repair of the oxidatively modified base 8-oxo-7,8-dihydroguanine (OG) and transcriptional activation has been documented in mammalian genes. Previously, we synthesized OG into the VEGF potential G-quadruplex sequence (PQS) in the coding strand of a luciferase promoter to identify that base excision repair (BER) unmasked the G-quadruplex (G4) fold for gene activation. In the present work, OG was site-specifically synthesized into a luciferase reporter plasmid to follow the time-dependent expression in mammalian cells when OG in the VEGF PQS context was located in the coding vs template strands of the luciferase promoter. Removal of OG from the coding strand by OG glycosylase-1 (OGG1)-mediated BER upregulated transcription. When OG was in the template strand in the VEGF

SUBMITTER: Fleming AM 

PROVIDER: S-EPMC5604463 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature