In this study, we found that knocking out HDGF in CRC cells leads to the accumulation of DNA DSBs and significantly increases the phosphorylation levels of DNA-PKcs S2056, ATM S1981, ATR T1989, and their downstream targets CHK1 S345 and CHK2 Thr68 (Figure 2A,B). Here, ATM is linked to colorectal carcinoma.