AP endonuclease 1 (Apex1) influences brain development linking oxidative stress and DNA repair

• DOI: 10.1038/s41419-019-1578-1
• Publication Date: 2019-04-25T08:05:07Z
• Authors: De-Sheng Pei; Pan-Pan Jia; Juan-Juan Luo; Wei Liu; Phyllis R. Strauss
• Keywords: 0303 health sciences; Guanine; DNA Repair; Brain; Zebrafish Proteins; Article; Morpholinos; Oxidative Stress; 03 medical and health sciences; DNA-(Apurinic or Apyrimidinic Site) Lyase; Animals; Tumor Suppressor Protein p53; Cyclic AMP Response Element-Binding Protein; Reactive Oxygen Species; DNA Polymerase beta; Zebrafish; Transcription Factors

Brain and neurons are particularly sensitive to reactive oxygen species (ROS). Oxidative damage from ROS results in increased 8-oxoguanine DNA followed by repair through the base excision (BER) pathway. We reported earlier that AP endonuclease 1 (Apex1) not only participates directly BER but also regulates transcription factor Creb1. Here, we investigated how Apex1 affects brain respond effectively oxidative during zebrafish development. Loss of resulted ROS, 8-oxoguanine, abasic sites as well loss Ogg1, which recognizes is required for its repair. Moreover, knock-down reduction expression several major proteins pathway (Polb Ogg1), it maldistribution four key factors (fezf2, otx2, egr2a, pax2a), leading abnormal These were independent p53 protein level. In contrast, exposure exogenous H2O2 along with other components, Taken together, these indicate stress when level was reduced, revealing a novel manages developing brain.