NOTCH1 is known to negatively regulate the DNA damage response, with phosphorylated H2AX (p-H2AX) serving as a marker of DNA damage and therapy resistance in CRC.25,26 In Ythdf1cki tumors, p-H2AX levels were lower than those in wild-type tumors, indicating reduced DNA damage. This evidence concerns the gene H2AX and colorectal carcinoma.