A correlation between DNA repair of the oxidatively modified base 8-oxo-7,8-dihydroguanine (OG) and gene activation has been observed in the <i>VEGF, TNF-α, SIRT1,</i> and <i>BCL2</i> genes.  A large fraction of gene promoters, including oncogenes, contain potential G-quadruplex (G4)-forming sequences, and these G-rich sequences are also sites prone to oxidative modification.  When OG and related lesions are formed in a G4 context, repair by the base excision repair pathway is interrupted by the ability of AP-endonuclease (APE1) to stall on G4s without completing repair; instead APE1 becomes a transcriptional regulator by recruiting activating transcription factors.  Biochemical, biophysical and cell-based assays have shed light on the molecular details of the protein partners involved in this response to DNA oxidation.  Implications for this behavior in terms of the interplay of base excision repair and gene expression will be discussed.  In this mechanism, G-quadruplexes in gene promoters serve as sensors of oxidative stress, and APE1 switches from its well-known BER role to that of a coordinator of transcription factors.

Linking DNA damage and repair to gene expression

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ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.