TEAD functions as conserved master regulator of DNA repair systems

DNA repair systems perform a crucial role in correcting DNA lesions to maintain genome stability. Whether the DNA repair machinery is coordinately regulated remains elusive. Here, we report that the TEAD family of transcription factors acts as a master regulator that orchestrates a transcriptional program that governs DNA repair in mammalian cells. Genetic inactivation in Teads increases DNA damage. When focused on the core genes in mismatch repair, we demonstrate that these genes are direct TEAD targets. Knockout of Tead1/4 induces a microsatellite instability (MSI) status in mouse colorectal tumors. Clinically, the low expressions of TEAD1/4 are associated with MSI status of colorectal cancer.