Fig. 8. Schematic diagram of how Apex1 responds to oxidative damage to regulate brain development via Creb1.

ROS result in oxidative damage to DNA, including increases in °G and AP sites, which enhance protein levels of Apex1. Increased Apex1 results in increased Creb1 that in turn enhances levels of BER pathway participants (Ogg1 and Polb), which together with Apex1 repair oxidatively damaged DNA. Meanwhile, other genes dependent on Creb1 are also upregulated, many involved in development, particularly brain development and function, including pax2, egr2a, fezf2, and otx2