ORC1 and cancer: Since over-expression of CDT1 or ORC1 is known to cause DNA re-replication32, 33 to trigger DNA damage response (DDR) and checkpoint controls in other cancer cell lines34, 35, we measured the levels of DDR biomarkers and found again that MLN4924 caused a time- and dose-dependent increase of phosphor-ATM, pCHK1, pCHK2, and γH2AX (Fig. 3a,b).