Prostate cancer (PCa), the second leading cause of death in American men, includes distinct genetic subtypes with distinct therapeutic vulnerabilities. TheDACH1gene encodes a winged helix/Forkhead DNA-binding protein that competes for binding to FOXM1 sites. Herein,DACH1gene deletion within the 13q21.31-q21.33 region occurs in up to 18% of human PCa and was associated with increased AR activity and poor prognosis. In prostate OncoMice, prostate-specific deletion of theDach1gene enhanced prostatic intraepithelial neoplasia (PIN), and was associated with increased TGFβ activity and DNA damage. ReducedDach1increased DNA damage in response to genotoxic stresses.DACH1was recruited to sites of DNA damage, augmenting recruitment of Ku70/Ku80. ReducedDach1expression was associated with increased homology directed repair and resistance to PARP inhibitors and TGFβ kinase inhibitors. ReducedDach1expression may define a subclass of PCa that warrants specific therapies.