Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis

Significance Dietary selenium and selenoproteins play important roles in regulating redox processes that impact human health. The human genome includes 25 genes for selenoproteins, which have diverse roles in redox homeostasis, thyroid hormone metabolism, endoplasmic reticulum quality control, selenium transport, and other functions. Selenoprotein H ( seph ) is a recently identified nucleolar oxidoreductase with DNA-binding properties whose function is not well understood. In this work, we used a unique combination of unbiased metabolomic and transcriptomic approaches in zebrafish to discover that seph is an essential regulator of redox homeostasis that regulates p53. In addition, we demonstrate the seph -deficient adults are prone to chemically induced carcinogenesis. Our results suggest that seph suppresses oxidative stress and DNA damage in the nucleolus.