Molecular dissection of the interaction between HIC1 and SIRT1

► HIC1 interacts with SIRT1 through its BTB/POZ and 4 Zinc fingers domains. ► SIRT1 interacts with HIC1 through its catalytic and C-terminal ESA domains. ► The ESA domain contains two Serine residues phosphorylated by CKII upon DNA-damages. ► TBCA, an inhibitor of CKII, inhibits the interaction between HIC1 and SIRT1. ► The acetylation/SUMOylation switch of HIC1 regulates the DNA damage response.