HSF4 is involved in DNA damage repair through regulation of Rad51

► HSF4 promotes DNA breaks repair through the regulation of Rad51 expression. ► HSF4 pathogenic mutations abolish the DNA damage repair ability of HSF4. ► Camptothecin inhibits the up-regulation of Rad51 levels by HSF4. ► Knock down of HSF4 in Zebrafish decrease Rad51 levels and DNA repair.