We propose that 53BP1-MDs mediated by cohesin-dependent chromatin dynamics contributes to CRC chemoresistance, and the strategies that inhibit the recruitment of ESCO2 to DBSs and/or reduce its acetyltransferase activity to disrupt the ring-like structure of 53BP1 may have therapeutic value in CRC radiotherapy and chemotherapy. Here, TP53BP1 is linked to colorectal carcinoma.